{"ID":78060,"post_author":"9208550","post_date":"2018-12-14 14:21:58","post_date_gmt":"0000-00-00 00:00:00","post_content":"","post_title":"LIMSjournal - Spring 2016","post_excerpt":"","post_status":"draft","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"","to_ping":"","pinged":"","post_modified":"2018-12-14 14:21:58","post_modified_gmt":"2018-12-14 19:21:58","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.limsforum.com\/?post_type=ebook&p=78060","menu_order":0,"post_type":"ebook","post_mime_type":"","comment_count":"0","filter":"","_ebook_metadata":{"enabled":"on","private":"0","guid":"51A6F9DA-80D0-4278-A308-D7D030912648","title":"LIMSjournal - Spring 2016","subtitle":"Volume 2, Issue 1","cover_theme":"nico_7","cover_image":"https:\/\/www.limsforum.com\/wp-content\/plugins\/rdp-ebook-builder\/pl\/cover.php?cover_style=nico_7&subtitle=Volume+2%2C+Issue+1&editor=Shawn+Douglas&title=LIMSjournal+-+Spring+2016&title_image=https%3A%2F%2Fs3.limsforum.com%2Fwww.limsforum.com%2Fwp-content%2Fuploads%2FFig4_Wenig_BMCBioinformatics2010_11.jpg&publisher=LabLynx+Press","editor":"Shawn Douglas","publisher":"LabLynx Press","author_id":"26","image_url":"","items":{"4eab7c6abfe5289f728109669eaa90ed_type":"article","4eab7c6abfe5289f728109669eaa90ed_title":"The need for informatics to support forensic pathology and death investigation (Levy 2015)","4eab7c6abfe5289f728109669eaa90ed_url":"https:\/\/www.limswiki.org\/index.php\/Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation","4eab7c6abfe5289f728109669eaa90ed_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:The need for informatics to support forensic pathology and death investigation\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nThe need for informatics to support forensic pathology and death investigationJournal\n \nJournal of Pathology InformaticsAuthor(s)\n \nLevy, BruceAuthor affiliation(s)\n \nUniversity of Illinois at ChicagoPrimary contact\n \nEmail: http:\/\/www.jpathinformatics.org (Requires login)Year published\n \n2015Volume and issue\n \n6Page(s)\n \n32DOI\n \n10.4103\/2153-3539.158907ISSN\n \n2045-2322Distribution license\n \nCreative Commons Attribution-NonCommercial-ShareAlike 3.0 UnportedWebsite\n \nhttp:\/\/www.jpathinformatics.orgDownload\n \nhttp:\/\/www.jpathinformatics.org\/temp\/JPatholInform6132-5990369_163823.pdf (PDF)\n\nContents\n\n1 Abstract \n2 Introduction \n3 What is clinical informatics? \n4 What is forensic pathology and medicine? \n5 Data collection in forensic pathology \n6 Effective use of forensic death investigation data \n\n6.1 Death certification \n6.2 Medical Examiners and Coroners Alert Project \n6.3 Medical Examiner and Coroner Information Sharing Program \n6.4 National Violent Death Reporting System \n6.5 National Missing and Unidentified Persons System \n\n\n7 Shortcomings of existing systems \n8 A path forward \n9 Conclusions \n10 Additional info \n11 References \n12 Notes \n\n\n\nAbstract \nAs a result of their practice of medicine, forensic pathologists create a wealth of data regarding the causes of and reasons for sudden, unexpected or violent deaths. This data have been effectively used to protect the health and safety of the general public in a variety of ways despite current and historical limitations. These limitations include the lack of data standards between the thousands of death investigation (DI) systems in the United States, rudimentary electronic information systems for DI, and the lack of effective communications and interfaces between these systems. Collaboration between forensic pathology and clinical informatics is required to address these shortcomings and a path forward has been proposed that will enable forensic pathology to maximize its effectiveness by providing timely and actionable information to public health and public safety agencies.\nKeywords: Clinical informatics, death investigation, forensic pathology, public health, public safety\n\nIntroduction \nClinical Informatics (CI) and Forensic Pathology would appear to be two subspecialties of medicine with little in common, as many equate informatics with the management of electronic medical records and forensics with the \"criminal\" investigation of homicides. These commonly held beliefs regarding forensics and informatics are simplistic and woefully incomplete. In reality, both fields are much broader, and there are opportunities for integration between forensics and informatics. Collaboration involving the expertise of the forensic pathologist in medicolegal death investigation (DI) and the skills of the clinical informatician to transform data into information can lead to the development of processes and systems that will better protect the health and safety of the public in an era of expanding threats from infectious disease, violent crime and terrorism.\n\nWhat is clinical informatics? \nClinical Informatics is a newly recognized subspecialty, with the first board examinations and certifications in 2013 and establishment of Accreditation Council for Graduate Medical Education accredited fellowships starting in 2014. CI is defined as \"the subspecialty of all medical specialties that transforms health care by analyzing, implementing, and evaluating information and communication systems to improve patient care, enhance access to care, advance individual and population health outcomes, and strengthen the clinician-patient relationship.\"[1] CI is commonly confused with Information Technology (IT), yet there is a distinct difference between these two fields. IT emphasizes the tools that are used for data manipulation while not being overly concerned with the data content. In contrast, CI's primary focus is on the data and considers IT as only one of many tools at its disposal.\nThere are two subdomains within the broad field of CI that are most relevant to forensics: Pathology informatics (PI) and Public health informatics.\nPathology Informatics is \"the study and management of information, information systems, and processes in Pathology.\"[2] This \"subspecialty\" of Pathology has grown to involve much more than the management of the huge volumes of data generated by anatomic pathology and the clinical laboratory. PI is involved with the entire testing process from the ordering of the test through presentation and interpretation of the results; in other words, the preanalytic, analytic and postanalytic phases of laboratory testing.[3]\nPublic health informatics is \"the systematic application of information, computer science and technology to public health practice, research, and learning.\"[4] Public health is focused on populations instead of individuals, prevention instead of treatment of disease, and government agencies instead of health care systems.[5] Public health systems work at local, state, national and global levels to both prevent morbidity and mortality utilizing multiple modalities and to address emergent situations such as infectious disease outbreaks when they occur.\n\nWhat is forensic pathology and medicine? \nForensic pathology is a subspecialty of pathology that concerns itself with the investigation of sudden, unexpected or violent deaths. While only formally recognized since the middle of the 20th Century, the origins of forensic pathology date back many centuries.[6] The major responsibility of the forensic pathologist is to determine the cause and manner of death for persons that fall under their jurisdiction. The forensic pathologist accomplishes this goal by correlating the data collected through conducting a death scene investigation, performing an autopsy, and ordering a variety of additional laboratory tests such as histology, toxicology, and microbiology. Forensic medicine is also involved with the examination and collection of evidence from living persons who are the victims of assault. The most common example of this in the United States is the examination of victims of sexual assault.[7]\nThere are two main DI systems in the United States, coroners and medical examiners. Both coroners and medical examiners are responsible for investigating sudden, unexpected or violent deaths and making rulings on the cause and manner of the death. Coroners represent an older system that was brought to the United States from England. Coroners are mostly elected officials with no specific training in DI or forensics. Medical examiners are an American system created about a century ago.[6] Medical examiners are all physicians (almost all have formal training in forensic pathology) and are appointed government officials.\n\nData collection in forensic pathology \nAs a result of their work, forensic health care professionals gather a large quantity of textual and image data about their patients. This data are not limited to histories, physical examination findings and laboratory results that parallel those collected in other fields of medicine, but also include data gathered at the scene of death and from law enforcement agencies investigating the death. This data are critical in assisting the forensic pathologist in determining the cause and manner of death. Frequently it is the investigative data from the scene instead of the physical findings of the autopsy that allows the forensic pathologist to distinguish an accident from a homicide or suicide.\nThis data have been historically collected in hard copy formats. While there has been progress toward collecting data in electronic formats in recent years, in 2011 approximately 18% of DI offices had no electronic case management system. Over half of the offices with electronic systems have idiosyncratic homegrown databases, many of them created in simple spreadsheet or database programs. Different data types (image, textual, laboratory results) are not often linked together by patient. For example, approximately 25% of both homegrown and vendor systems do not have direct access to scene and autopsy images.[8]\nThere are few interfaces between existing DI information systems and the information systems of law enforcement, supporting laboratories or public health. Toxicology laboratory results, which are critical in a large percentage of forensic deaths, are still submitted as paper requests and received as paper reports, instead of through a bidirectional interface between the laboratory and medical examiner information systems. Forensic pathologists manually enter cause of death data both into their own office's information system and their state's electronic death certificate. This represents both duplications of effort and a source for the increased incidence of transcription errors.\nSolving this issue would appear to be simple, but is complicated by a variety of political, logistical and financial challenges.\nThere are approximately 2,000 distinct DI systems in the United States. In 2004, only sixteen states had a centralized statewide medical examiner system. The other states had a combination of county coroner and\/or medical examiner systems. These county-based systems can represent large cities, medium suburban areas, or small rural communities. Over 80% of the DI systems are county coroner systems in small to medium-sized jurisdictions. Resources are heavily concentrated in a few large systems. Most offices serving jurisdictions of 25,000 persons or less have only one full-time equivalent and median annual operating budgets of under $20,000.[9]\nThis large number of DI systems of various sizes and with differing access to resources represents a challenge to consistent data collection. Larger DI offices with greater resources employ specially trained death investigators to systematically collect information regarding reported deaths, and are more likely to use electronic information systems to collect the information. Smaller offices typically rely on law enforcement, whose investigative focus is on the investigation of crime rather than death, and receive paper investigative reports that may or may not be scanned or integrated into an electronic system.\nThere are currently no standards regarding the structuring of data or interfaces for electronic DI databases. As a result, there is no effective way to transfer information between different agencies either in the same jurisdiction or between jurisdictions. This not only impedes efficient operations on a day-to-day basis, but also is crippling during multijurisdictional emergencies, such as mass fatality incidents or infectious disease epidemics, where the free flow of information is critical.\nDespite well-documented issues regarding the lack of data standards and inconsistencies between DI offices there has been little political will to invest the resources to address these deficiencies. The 2009 National Academy of Sciences Report on Forensic Science recommended that DI offices should have case information databases that would enable trend analysis of deaths for public health and safety purposes and continuous quality improvement.[10] Yet there has been a little improvement or significant political will to provide funding or standards for DI offices since that time.[11]\n\nEffective use of forensic death investigation data \nThere are numerous examples of how information generated as a result of the work of forensic pathologists has been utilized in meaningful ways.\n\nDeath certification \nThe collection and compilation of the cause of death statements from death certificates have long been used by public health for epidemiology studies, disease surveillance, and determining where to focus public health resources. Unfortunately, the causes of death on these certificates are incorrect as much as half of the time. This is true even for common causes of death such as cardiovascular disease and cancer. Common errors include incorrect causes of death, nonspecific causes of death, and the inclusion of irrelevant diseases as contributing to death.[12][13][14]\nForensic pathologists provide approximately 20% of the death certificates in the United States.[15] As they are specifically trained in the proper completion of death certificates, the accuracy of information provided is greatly increased as long as a full autopsy had been performed. However, due to limited financial and logistical resources in most DI offices, many natural deaths and a significant percentage of noncriminal violent deaths may not be autopsied. It has been well documented that forensic pathologists produce a significant number of errors in death certification when external examinations are performed instead of an autopsy.[16][17]\nDeath certificate information is not only used by local, state and national public health departments to help set public health initiatives, but is also used by other agencies reviewing deaths from specific causes. The United States Department of Transportation studies transportation-related deaths through their Fatality Analysis Reporting System, and this has resulted in many improvements in the designs of motor vehicles and roadways. Similarly, the United States Department of Labor's Census of Fatal Occupational Injuries and the National Institute for Occupational Safety and Health's Traumatic Occupational Injuries Research and Prevention Program have effectively used death certificate data to improve workplace safety.[18]\n\nMedical Examiners and Coroners Alert Project \nThe United States Consumer Product Safety Commission's (CPSC) Medical Examiners and Coroners Alert Project (MECAP) was created in 1976 as a quick alert system to report deaths where consumer products played a significant role in the death. Excluded from MECAP are deaths involving automobiles (but not off-road vehicles such as All-Terrain Vehicles), firearms (except air rifles and BB guns), foods, cosmetics, medical devices, aircraft, boats and boating equipment, and products used solely in industrial or commercial environments. There have been over 9,000 \"valuable cases\" reported that resulted in product recalls or product standards development. The CPSC's website provides detailed information regarding, which deaths should be reported. The program is voluntary and requires the medical examiner or coroner to proactively identify potential cases and take the time to report them. Reports can be accepted by phone, mail, fax or through a linked website.[19]\n\nMedical Examiner and Coroner Information Sharing Program \nThe Medical Examiner and Coroner Information Sharing Program (MECISP) was created by the Centers for Disease Control and Prevention in 1986. This was envisioned as a national system to collect and analyze information on medical examiner and coroner deaths to enable public health to quickly identify and understand the causes of sudden and unexpected deaths, leading to strategies to reduce mortality.[20] As the first decade of data collection contained data in the many different formats used by the offices voluntarily contributing to the program, MECISP set a goal of standardizing data collection by creating guidelines for creating forensic data management programs and a standardized DI data set.[21] Despite some success, the MECISP program was essentially defunded by the mid-2000's and is no longer functional.\n\nNational Violent Death Reporting System \nThe National Violent Death Reporting System (NVDRS) is another program created by the Centers for Disease Control and Prevention in 2002 to collect and study the causes of homicides and suicides. The premise is that all these deaths are potentially preventable and that comprehensive data collection will facilitate the creation of violence prevention strategies. NVDRS is a state-based system designed to combine data from multiple sources (death certificates, medical examiner and coroner reports, law enforcement reports, and crime laboratories) into a single searchable database. Initially deployed in 16 states, it is now collecting data from 32 states with the ultimate goal of covering the entire Unites States. In 2013 NVDRS went to a web-based system for easy accessibility to the data. The program has had many successes in studying deaths in children due to maltreatment, suicides among soldiers, intimate partner homicides, elderly suicides and geographic distributions of violence.[22][23][24][25]\n\nNational Missing and Unidentified Persons System \nThe issues of missing persons and unidentified human remains have been described as a silent mass disaster. At any given time, there are over 100,000 active missing persons cases and over 40,000 unidentified human remains in the United States. Historically there have been multiple databases at state and federal levels containing a combination of unique and overlapping information attempting to address the problem, but creating a logistical nightmare for law enforcement agencies and medical examiners to match missing persons with unidentified remains.[26]\nIn response, the United States Department of Justice created the National Missing and Unidentified Persons System (NamUs). NamUs has three main databases: a missing persons database in which families or law enforcement may enter information regarding missing persons and follow cases; an unidentified persons database where medical examiners and coroners may enter information on unidentified persons and the general public can search; and an unclaimed persons database for persons who have been identified but where family has not been found. The missing and unidentified person's databases interact to match information when entered into either system. As of October 2014, NamUs has resolved approximately 9000 cases of missing or unidentified persons.[27]\n\nShortcomings of existing systems \nWhile all of the above systems and programs have been effective, they have common shortcomings. With the exception of death certificates, the entry of information into these disparate databases is voluntary on the part of medical examiners and coroners. Much of the data entry is manual or semi-automated, requiring significant human effort to accomplish. These two factors complicated by the limited resources of many DI systems leads to partial participation, even when offices would prefer to contribute.\nDespite the recognition that there need to be standards regarding what data are collected and how it is classified and organized in a DI database, little progress has been made on this front. The few electronic communications of information directly from forensic offices to outside agencies are in the form of customized reports. There is currently no communication standard that would allow information to flow freely to, from and between DI electronic information systems, even when they are provided by the same vendor. These issues hinder the ability of forensic pathologists to effectively transform the data they are collecting into actionable information that would better inform public health and public safety agencies.\n\nA path forward \nA prerequisite for improving the current situation is recognition in the forensic pathology community of the value of their data beyond the individual case. The examples of the government-based data sharing programs described above support the opinion that it is unlikely the federal government will solve the overarching problem of data consistency and analysis in forensic pathology. DI organizations, such as the National Association of Medical Examiners (NAME) and the International Association of Coroners and Medical Examiners (IACME), need to take leadership of this issue. Both of these professional organizations are dedicated to advancing DI and have existing standards for accreditation of offices.[28][29] While these groups are experts in the area of DI, they lack the necessary informatics expertise that will ensure success.\nThe Association for Pathology Informatics (API), a professional organization of pathologists with expertise in informatics, is the obvious partner for this endeavor. API's focus on data standards in pathology and the informatics education of pathologists complements the focus on standards and education by NAME and IACME for forensic pathology and DI. API has a history of reaching out to collaborate with other professional organizations in pathology and CI, and already works with government and industry groups in the development of data and communication standards.[30]\nCollaboration between these groups could address the challenges of sharing, merging and analyzing data from the large number of DI systems, each with their unique methods of organizing their data. Rather than attempt to start with a comprehensive solution, it may be advantageous to choose a handful of smaller projects to demonstrate value and to work through any issues that might become apparent. Data fields that are more likely to be consistent across different DI offices, such as basic demographics, cause of death and manner of death, are an obvious first step in this process. Toxicology and other laboratory results may be another potential \"low hanging fruit\" for collection and analysis. With some early successes, it will be easier to sit down and develop a more comprehensive solution, which should also include standards for the next generation of DI information systems.\nThe key is to develop a process by which data can be automatically transferred through an electronic interface from the individual DI office systems into a single database and subsequently back out to other systems for analysis. This includes several challenges that need to be addressed. Data fields in different systems may have different names, data types and conventions for expressing the data. For example, a field for manner of death may not only be named differently in different systems, but might be expressed as free text fields, defined text fields, abbreviations or even a numerical or symbolic representation for each manner of death. While it may seem like an insurmountable problem, the development of data standards has been accomplished in other areas of health care and is attainable for forensic pathology.[31] A communication standard for transmitting the data would also need to be selected or developed. A communication standard ensures that the receiving system understands the message from the sending system and can place the communicated data into the proper fields. One commonly used an example for health care is Health Level 7. Another major issue to address is the security of the data, especially given the sensitive nature of this subset of personal health information.\nOnce this data are collected, policies regarding storage and access to the data for analysis and study will need to be created. There are currently many examples of secure data storage \"in the cloud\" that could be utilized. Some of this data can have great value if freely accessible on the web. NamUS is an excellent example of the power of open information. NVDRS has a mixture of data that is freely accessible or restricted based on whether the data may lead to disclosure of the identity of victims or suspects, and may serve as a guideline. Another issue to consider is the needs of law enforcement to restrict access to data for cases that are actively being investigated.\nIn addition to the expertise of forensic pathologists and pathology informaticians, this effort would require significant financial support, including; travel for forensic and informatics subject matter experts to design the project and define the standards, creation and support for the database, storage costs for the data, design of mechanisms to access or transfer the data for study, and general ongoing support for the project. Given the value of this data to many different government agencies and departments, it is reasonable to pursue funding through these agencies. It should be understood that the control over the collected data would reside with the professional organizations and not with the government itself since the subject matter experts are the best custodians of the data.\n\nConclusions \nForensic pathology contains a wealth of information that is invaluable for many purposes. The current spectrum of information systems available to medical examiners and coroners are woefully inadequate to support the efficient use of this data. Data standards for DI and forensic information systems need to be developed. Standard communication protocols would enable the efficient automatic transfer of this data directly from medical examiner and coroner offices to national programs such as NVDRS and NamUs, to other public health, public safety and homeland security surveillance systems, and increase the timeliness and usability of this information. Clinical\/PI needs to collaborate with forensic pathology to create systems to better utilize DI data to protect the public health and safety.\n\nAdditional info \nSource of Support: None\r\n\nConflict of Interest: None\n\nReferences \n\n\n\u2191 Accreditation Council for Graduate Medical Education (03 February 2014). \"ACGME Program Requirements for Graduate Medical Education in Clinical Informatics\" (PDF). http:\/\/www.acgme.org\/acgmeweb\/Portals\/0\/PFAssets\/ProgramRequirements\/381_clinical_informatics_02032014.pdf . Retrieved 30 December 2014 .   \n\n\u2191 Levy, B.P.; McClintock, D.S.; Lee, R.E. et al. (2012). \"Different tracks for pathology informatics fellowship training: Experiences of and input from trainees in a large multisite fellowship program\". Journal of Pathology Informatics 3: 30. doi:10.4103\/2153-3539.100362. PMC PMC3445299. 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PMID 16948511.   \n\n\u2191 Directorate for Epidemiology. \"Medical Examiners and Coroners Alert Project\" (PDF). MECAP News. U.S. Consumer Product Safety Commission. http:\/\/www.cpsc.gov\/\/Global\/Research-and-Statistics\/MECAP\/MECAP%20News%20-%20General%20Information.pdf . Retrieved 30 December 2014 .   \n\n\u2191 \"Medical examiner\/coroner information-sharing program\". The American Journal of Forensic Medicine and Pathology 10 (1): 88\u201389. 1989. PMID 2539009.   \n\n\u2191 Hanzlick, R. (1997). \"Centers for Disease Control and Prevention's Medical Examiner\/Coroner Information Sharing Program (MecISP)\". Journal of Forensic Sciences 42 (3): 531\u2013532. https:\/\/www.ncjrs.gov\/App\/Publications\/abstract.aspx?ID=172060 .   \n\n\u2191 \"National Violent Death Reporting System\". Centers for Disease Control and Prevention. 08 December 2014. http:\/\/www.cdc.gov\/violenceprevention\/nvdrs\/ . Retrieved 30 December 2014 .   \n\n\u2191 Klevens, J.; Leeb, R.T. (2010). \"Child maltreatment fatalities in children under 5: Findings from the National Violence Death Reporting System\". Child Abuse & Neglect 34 (4): 262\u2013266. doi:10.1016\/j.chiabu.2009.07.005. PMID 20304491.   \n\n\u2191 Smith, S.G.; Fowler, K.A.; Niolon, P.H. (2014). \"Intimate partner homicide and corollary victims in 16 states: National Violent Death Reporting System, 2003-2009\". American Journal of Public Health 104 (3): 461\u2013466. doi:10.2105\/AJPH.2013.301582. PMID 24432943.   \n\n\u2191 Parks, S.E.; Johnson, L.L.; McDaniel, D.D.; Gladden, M. (2014). \"Surveillance for Violent Deaths \u2014 National Violent Death Reporting System, 16 States, 2010\". Morbidity and Mortality Weekly Report: Surveillance Summaries 63 (SS01): 461\u2013466. http:\/\/www.cdc.gov\/mmwr\/preview\/mmwrhtml\/ss6301a1.htm .   \n\n\u2191 Ritter, N. (2007). \"Missing persons and unidentified remains: The nation\u2032s silent mass disaster\". National Institute of Justice Journal (256). http:\/\/www.nij.gov\/journals\/256\/pages\/missing-persons.aspx .   \n\n\u2191 Office of Justice Programs. \"National Missing and Unidentified Persons System\". United States Department of Justice. http:\/\/www.namus.gov\/index.htm . Retrieved 30 December 2014 .   \n\n\u2191 \"National Association of Medical Examiners Web Site\". National Association of Medical Examiners. http:\/\/www.thename.org\/ . Retrieved 01 April 2015 .   \n\n\u2191 \"International Association of Coroners and Medical Examiners - Home\". International Association of Coroners and Medical Examiners. http:\/\/www.theiacme.com\/ . Retrieved 01 April 2015 .   \n\n\u2191 \"Association for Pathology Informatics\". Association for Pathology Informatics. http:\/\/www.pathologyinformatics.org\/ . Retrieved 01 April 2015 .   \n\n\u2191 Hammond, W.E.; Jaffe, C.; Cimino, J.J.; Huff, S.M. (2014). \"Standards in biomedical informatics\". In Shortliffe, E.H.; Cimino, J.J.. Biomedical Informatics: Computer Applications in Health Care and Biomedicine. pp. 211\u2013253. doi:10.1007\/978-1-4471-4474-8. ISBN 9781447144731.   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\">https:\/\/www.limswiki.org\/index.php\/Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on forensic science\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 28 March 2016, at 16:02.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 1,847 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","4eab7c6abfe5289f728109669eaa90ed_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_The_need_for_informatics_to_support_forensic_pathology_and_death_investigation skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:The need for informatics to support forensic pathology and death investigation<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>As a result of their practice of medicine, <a href=\"https:\/\/www.limswiki.org\/index.php\/Forensic_science\" title=\"Forensic science\" target=\"_blank\" class=\"wiki-link\" data-key=\"415d36a7b65494677b6d2873d5febec1\">forensic<\/a> pathologists create a wealth of data regarding the causes of and reasons for sudden, unexpected or violent deaths. This data have been effectively used to protect the health and safety of the general public in a variety of ways despite current and historical limitations. These limitations include the lack of data standards between the thousands of death investigation (DI) systems in the United States, rudimentary electronic information systems for DI, and the lack of effective communications and interfaces between these systems. Collaboration between forensic pathology and <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_informatics\" title=\"Health informatics\" target=\"_blank\" class=\"wiki-link\" data-key=\"055eb51f53cfdbacc08ed150b266c9f4\">clinical informatics<\/a> is required to address these shortcomings and a path forward has been proposed that will enable forensic pathology to maximize its effectiveness by providing timely and actionable <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" target=\"_blank\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> to public health and public safety agencies.\n<\/p><p><b>Keywords:<\/b> Clinical informatics, death investigation, forensic pathology, public health, public safety\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>Clinical Informatics (CI) and Forensic Pathology would appear to be two subspecialties of medicine with little in common, as many equate <a href=\"https:\/\/www.limswiki.org\/index.php\/Informatics\" title=\"Informatics\" class=\"mw-disambig wiki-link\" target=\"_blank\" data-key=\"ea0ff624ac3a644c35d2b51d39047bdf\">informatics<\/a> with the management of <a href=\"https:\/\/www.limswiki.org\/index.php\/Electronic_medical_record\" title=\"Electronic medical record\" target=\"_blank\" class=\"wiki-link\" data-key=\"99a695d2af23397807da0537d29d0be7\">electronic medical records<\/a> and <a href=\"https:\/\/www.limswiki.org\/index.php\/Forensic_science\" title=\"Forensic science\" target=\"_blank\" class=\"wiki-link\" data-key=\"415d36a7b65494677b6d2873d5febec1\">forensics<\/a> with the \"criminal\" investigation of homicides. These commonly held beliefs regarding forensics and informatics are simplistic and woefully incomplete. In reality, both fields are much broader, and there are opportunities for integration between forensics and informatics. Collaboration involving the expertise of the forensic pathologist in medicolegal death investigation (DI) and the skills of the clinical informatician to transform data into information can lead to the development of processes and systems that will better protect the health and safety of the public in an era of expanding threats from infectious disease, violent crime and terrorism.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"What_is_clinical_informatics.3F\">What is clinical informatics?<\/span><\/h2>\n<p>Clinical Informatics is a newly recognized subspecialty, with the first board examinations and certifications in 2013 and establishment of Accreditation Council for Graduate Medical Education accredited fellowships starting in 2014. CI is defined as \"the subspecialty of all medical specialties that transforms health care by analyzing, implementing, and evaluating information and communication systems to improve patient care, enhance access to care, advance individual and population health outcomes, and strengthen the clinician-patient relationship.\"<sup id=\"rdp-ebb-cite_ref-ACGMEProg14_1-0\" class=\"reference\"><a href=\"#cite_note-ACGMEProg14-1\" rel=\"external_link\">[1]<\/a><\/sup> CI is commonly confused with Information Technology (IT), yet there is a distinct difference between these two fields. IT emphasizes the tools that are used for data manipulation while not being overly concerned with the data content. In contrast, CI's primary focus is on the data and considers IT as only one of many tools at its disposal.\n<\/p><p>There are two subdomains within the broad field of CI that are most relevant to forensics: Pathology informatics (PI) and <a href=\"https:\/\/www.limswiki.org\/index.php\/Public_health_informatics\" title=\"Public health informatics\" target=\"_blank\" class=\"wiki-link\" data-key=\"f0372a80f101e9f6fd00490dc1ebcedd\">Public health informatics<\/a>.\n<\/p><p>Pathology Informatics is \"the study and management of information, information systems, and processes in Pathology.\"<sup id=\"rdp-ebb-cite_ref-LevyDiff12_2-0\" class=\"reference\"><a href=\"#cite_note-LevyDiff12-2\" rel=\"external_link\">[2]<\/a><\/sup> This \"subspecialty\" of Pathology has grown to involve much more than the management of the huge volumes of data generated by <a href=\"https:\/\/www.limswiki.org\/index.php\/Anatomical_pathology\" title=\"Anatomical pathology\" target=\"_blank\" class=\"wiki-link\" data-key=\"5668db6faf37e8c1432a1d7953f30cb7\">anatomic pathology<\/a> and the <a href=\"https:\/\/www.limswiki.org\/index.php\/Clinical_laboratory\" title=\"Clinical laboratory\" target=\"_blank\" class=\"wiki-link\" data-key=\"307bcdf1bdbcd1bb167cee435b7a5463\">clinical laboratory<\/a>. PI is involved with the entire testing process from the ordering of the test through presentation and interpretation of the results; in other words, the preanalytic, analytic and postanalytic phases of <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" target=\"_blank\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratory<\/a> testing.<sup id=\"rdp-ebb-cite_ref-McClintockACore12_3-0\" class=\"reference\"><a href=\"#cite_note-McClintockACore12-3\" rel=\"external_link\">[3]<\/a><\/sup>\n<\/p><p>Public health informatics is \"the systematic application of information, computer science and technology to public health practice, research, and learning.\"<sup id=\"rdp-ebb-cite_ref-YasnoffPublic00_4-0\" class=\"reference\"><a href=\"#cite_note-YasnoffPublic00-4\" rel=\"external_link\">[4]<\/a><\/sup> Public health is focused on populations instead of individuals, prevention instead of treatment of disease, and government agencies instead of health care systems.<sup id=\"rdp-ebb-cite_ref-MagnusonPublic14_5-0\" class=\"reference\"><a href=\"#cite_note-MagnusonPublic14-5\" rel=\"external_link\">[5]<\/a><\/sup> Public health systems work at local, state, national and global levels to both prevent morbidity and mortality utilizing multiple modalities and to address emergent situations such as infectious disease outbreaks when they occur.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"What_is_forensic_pathology_and_medicine.3F\">What is forensic pathology and medicine?<\/span><\/h2>\n<p>Forensic pathology is a subspecialty of pathology that concerns itself with the investigation of sudden, unexpected or violent deaths. While only formally recognized since the middle of the 20th Century, the origins of forensic pathology date back many centuries.<sup id=\"rdp-ebb-cite_ref-SpitzHist06_6-0\" class=\"reference\"><a href=\"#cite_note-SpitzHist06-6\" rel=\"external_link\">[6]<\/a><\/sup> The major responsibility of the forensic pathologist is to determine the cause and manner of death for persons that fall under their jurisdiction. The forensic pathologist accomplishes this goal by correlating the data collected through conducting a death scene investigation, performing an autopsy, and ordering a variety of additional laboratory tests such as histology, toxicology, and microbiology. Forensic medicine is also involved with the examination and collection of evidence from living persons who are the victims of assault. The most common example of this in the United States is the examination of victims of sexual assault.<sup id=\"rdp-ebb-cite_ref-DOJANat13_7-0\" class=\"reference\"><a href=\"#cite_note-DOJANat13-7\" rel=\"external_link\">[7]<\/a><\/sup>\n<\/p><p>There are two main DI systems in the United States, coroners and medical examiners. Both coroners and medical examiners are responsible for investigating sudden, unexpected or violent deaths and making rulings on the cause and manner of the death. Coroners represent an older system that was brought to the United States from England. Coroners are mostly elected officials with no specific training in DI or forensics. Medical examiners are an American system created about a century ago.<sup id=\"rdp-ebb-cite_ref-SpitzHist06_6-1\" class=\"reference\"><a href=\"#cite_note-SpitzHist06-6\" rel=\"external_link\">[6]<\/a><\/sup> Medical examiners are all physicians (almost all have formal training in forensic pathology) and are appointed government officials.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Data_collection_in_forensic_pathology\">Data collection in forensic pathology<\/span><\/h2>\n<p>As a result of their work, forensic health care professionals gather a large quantity of textual and image data about their patients. This data are not limited to histories, physical examination findings and laboratory results that parallel those collected in other fields of medicine, but also include data gathered at the scene of death and from law enforcement agencies investigating the death. This data are critical in assisting the forensic pathologist in determining the cause and manner of death. Frequently it is the investigative data from the scene instead of the physical findings of the autopsy that allows the forensic pathologist to distinguish an accident from a homicide or suicide.\n<\/p><p>This data have been historically collected in hard copy formats. While there has been progress toward collecting data in electronic formats in recent years, in 2011 approximately 18% of DI offices had no electronic case management system. Over half of the offices with electronic systems have idiosyncratic homegrown databases, many of them created in simple spreadsheet or database programs. Different data types (image, textual, laboratory results) are not often linked together by patient. For example, approximately 25% of both homegrown and vendor systems do not have direct access to scene and autopsy images.<sup id=\"rdp-ebb-cite_ref-LevyImp13_8-0\" class=\"reference\"><a href=\"#cite_note-LevyImp13-8\" rel=\"external_link\">[8]<\/a><\/sup>\n<\/p><p>There are few interfaces between existing DI information systems and the information systems of law enforcement, supporting laboratories or public health. Toxicology laboratory results, which are critical in a large percentage of forensic deaths, are still submitted as paper requests and received as paper reports, instead of through a bidirectional interface between the laboratory and medical examiner information systems. Forensic pathologists manually enter cause of death data both into their own office's information system and their state's electronic death certificate. This represents both duplications of effort and a source for the increased incidence of transcription errors.\n<\/p><p>Solving this issue would appear to be simple, but is complicated by a variety of political, logistical and financial challenges.\n<\/p><p>There are approximately 2,000 distinct DI systems in the United States. In 2004, only sixteen states had a centralized statewide medical examiner system. The other states had a combination of county coroner and\/or medical examiner systems. These county-based systems can represent large cities, medium suburban areas, or small rural communities. Over 80% of the DI systems are county coroner systems in small to medium-sized jurisdictions. Resources are heavily concentrated in a few large systems. Most offices serving jurisdictions of 25,000 persons or less have only one full-time equivalent and median annual operating budgets of under $20,000.<sup id=\"rdp-ebb-cite_ref-DOJMed07_9-0\" class=\"reference\"><a href=\"#cite_note-DOJMed07-9\" rel=\"external_link\">[9]<\/a><\/sup>\n<\/p><p>This large number of DI systems of various sizes and with differing access to resources represents a challenge to consistent data collection. Larger DI offices with greater resources employ specially trained death investigators to systematically collect information regarding reported deaths, and are more likely to use electronic information systems to collect the information. Smaller offices typically rely on law enforcement, whose investigative focus is on the investigation of crime rather than death, and receive paper investigative reports that may or may not be scanned or integrated into an electronic system.\n<\/p><p>There are currently no standards regarding the structuring of data or interfaces for electronic DI databases. As a result, there is no effective way to transfer information between different agencies either in the same jurisdiction or between jurisdictions. This not only impedes efficient operations on a day-to-day basis, but also is crippling during multijurisdictional emergencies, such as mass fatality incidents or infectious disease epidemics, where the free flow of information is critical.\n<\/p><p>Despite well-documented issues regarding the lack of data standards and inconsistencies between DI offices there has been little political will to invest the resources to address these deficiencies. The 2009 National Academy of Sciences Report on Forensic Science recommended that DI offices should have case information databases that would enable trend analysis of deaths for public health and safety purposes and continuous quality improvement.<sup id=\"rdp-ebb-cite_ref-CommitteeMed09_10-0\" class=\"reference\"><a href=\"#cite_note-CommitteeMed09-10\" rel=\"external_link\">[10]<\/a><\/sup> Yet there has been a little improvement or significant political will to provide funding or standards for DI offices since that time.<sup id=\"rdp-ebb-cite_ref-ThompsonTheReal11_11-0\" class=\"reference\"><a href=\"#cite_note-ThompsonTheReal11-11\" rel=\"external_link\">[11]<\/a><\/sup>\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Effective_use_of_forensic_death_investigation_data\">Effective use of forensic death investigation data<\/span><\/h2>\n<p>There are numerous examples of how information generated as a result of the work of forensic pathologists has been utilized in meaningful ways.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Death_certification\">Death certification<\/span><\/h3>\n<p>The collection and compilation of the cause of death statements from death certificates have long been used by public health for epidemiology studies, disease surveillance, and determining where to focus public health resources. Unfortunately, the causes of death on these certificates are incorrect as much as half of the time. This is true even for common causes of death such as cardiovascular disease and cancer. Common errors include incorrect causes of death, nonspecific causes of death, and the inclusion of irrelevant diseases as contributing to death.<sup id=\"rdp-ebb-cite_ref-CambridgeTheAcc10_12-0\" class=\"reference\"><a href=\"#cite_note-CambridgeTheAcc10-12\" rel=\"external_link\">[12]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-SnyderRed14_13-0\" class=\"reference\"><a href=\"#cite_note-SnyderRed14-13\" rel=\"external_link\">[13]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-GermanTheAcc11_14-0\" class=\"reference\"><a href=\"#cite_note-GermanTheAcc11-14\" rel=\"external_link\">[14]<\/a><\/sup>\n<\/p><p>Forensic pathologists provide approximately 20% of the death certificates in the United States.<sup id=\"rdp-ebb-cite_ref-ParrishAss95_15-0\" class=\"reference\"><a href=\"#cite_note-ParrishAss95-15\" rel=\"external_link\">[15]<\/a><\/sup> As they are specifically trained in the proper completion of death certificates, the accuracy of information provided is greatly increased as long as a full autopsy had been performed. However, due to limited financial and logistical resources in most DI offices, many natural deaths and a significant percentage of noncriminal violent deaths may not be autopsied. It has been well documented that forensic pathologists produce a significant number of errors in death certification when external examinations are performed instead of an autopsy.<sup id=\"rdp-ebb-cite_ref-AsnaesUn80_16-0\" class=\"reference\"><a href=\"#cite_note-AsnaesUn80-16\" rel=\"external_link\">[16]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-NashelskyAcc03_17-0\" class=\"reference\"><a href=\"#cite_note-NashelskyAcc03-17\" rel=\"external_link\">[17]<\/a><\/sup>\n<\/p><p>Death certificate information is not only used by local, state and national public health departments to help set public health initiatives, but is also used by other agencies reviewing deaths from specific causes. The United States Department of Transportation studies transportation-related deaths through their Fatality Analysis Reporting System, and this has resulted in many improvements in the designs of motor vehicles and roadways. Similarly, the United States Department of Labor's Census of Fatal Occupational Injuries and the National Institute for Occupational Safety and Health's Traumatic Occupational Injuries Research and Prevention Program have effectively used death certificate data to improve workplace safety.<sup id=\"rdp-ebb-cite_ref-HanzlickMed06_18-0\" class=\"reference\"><a href=\"#cite_note-HanzlickMed06-18\" rel=\"external_link\">[18]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Medical_Examiners_and_Coroners_Alert_Project\">Medical Examiners and Coroners Alert Project<\/span><\/h3>\n<p>The United States Consumer Product Safety Commission's (CPSC) Medical Examiners and Coroners Alert Project (MECAP) was created in 1976 as a quick alert system to report deaths where consumer products played a significant role in the death. Excluded from MECAP are deaths involving automobiles (but not off-road vehicles such as All-Terrain Vehicles), firearms (except air rifles and BB guns), foods, cosmetics, medical devices, aircraft, boats and boating equipment, and products used solely in industrial or commercial environments. There have been over 9,000 \"valuable cases\" reported that resulted in product recalls or product standards development. The CPSC's website provides detailed information regarding, which deaths should be reported. The program is voluntary and requires the medical examiner or coroner to proactively identify potential cases and take the time to report them. Reports can be accepted by phone, mail, fax or through a linked website.<sup id=\"rdp-ebb-cite_ref-DirectorateMed_19-0\" class=\"reference\"><a href=\"#cite_note-DirectorateMed-19\" rel=\"external_link\">[19]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Medical_Examiner_and_Coroner_Information_Sharing_Program\">Medical Examiner and Coroner Information Sharing Program<\/span><\/h3>\n<p>The Medical Examiner and Coroner Information Sharing Program (MECISP) was created by the Centers for Disease Control and Prevention in 1986. This was envisioned as a national system to collect and analyze information on medical examiner and coroner deaths to enable public health to quickly identify and understand the causes of sudden and unexpected deaths, leading to strategies to reduce mortality.<sup id=\"rdp-ebb-cite_ref-Medical89_20-0\" class=\"reference\"><a href=\"#cite_note-Medical89-20\" rel=\"external_link\">[20]<\/a><\/sup> As the first decade of data collection contained data in the many different formats used by the offices voluntarily contributing to the program, MECISP set a goal of standardizing data collection by creating guidelines for creating forensic data management programs and a standardized DI data set.<sup id=\"rdp-ebb-cite_ref-HanzlickCenters97_21-0\" class=\"reference\"><a href=\"#cite_note-HanzlickCenters97-21\" rel=\"external_link\">[21]<\/a><\/sup> Despite some success, the MECISP program was essentially defunded by the mid-2000's and is no longer functional.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"National_Violent_Death_Reporting_System\">National Violent Death Reporting System<\/span><\/h3>\n<p>The National Violent Death Reporting System (NVDRS) is another program created by the Centers for Disease Control and Prevention in 2002 to collect and study the causes of homicides and suicides. The premise is that all these deaths are potentially preventable and that comprehensive data collection will facilitate the creation of violence prevention strategies. NVDRS is a state-based system designed to combine data from multiple sources (death certificates, medical examiner and coroner reports, law enforcement reports, and crime laboratories) into a single searchable database. Initially deployed in 16 states, it is now collecting data from 32 states with the ultimate goal of covering the entire Unites States. In 2013 NVDRS went to a web-based system for easy accessibility to the data. The program has had many successes in studying deaths in children due to maltreatment, suicides among soldiers, intimate partner homicides, elderly suicides and geographic distributions of violence.<sup id=\"rdp-ebb-cite_ref-CDCInj14_22-0\" class=\"reference\"><a href=\"#cite_note-CDCInj14-22\" rel=\"external_link\">[22]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-KlevensChild10_23-0\" class=\"reference\"><a href=\"#cite_note-KlevensChild10-23\" rel=\"external_link\">[23]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-SmithInt14_24-0\" class=\"reference\"><a href=\"#cite_note-SmithInt14-24\" rel=\"external_link\">[24]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-ParksSurv14_25-0\" class=\"reference\"><a href=\"#cite_note-ParksSurv14-25\" rel=\"external_link\">[25]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"National_Missing_and_Unidentified_Persons_System\">National Missing and Unidentified Persons System<\/span><\/h3>\n<p>The issues of missing persons and unidentified human remains have been described as a silent mass disaster. At any given time, there are over 100,000 active missing persons cases and over 40,000 unidentified human remains in the United States. Historically there have been multiple databases at state and federal levels containing a combination of unique and overlapping information attempting to address the problem, but creating a logistical nightmare for law enforcement agencies and medical examiners to match missing persons with unidentified remains.<sup id=\"rdp-ebb-cite_ref-RitterMiss07_26-0\" class=\"reference\"><a href=\"#cite_note-RitterMiss07-26\" rel=\"external_link\">[26]<\/a><\/sup>\n<\/p><p>In response, the United States Department of Justice created the National Missing and Unidentified Persons System (NamUs). NamUs has three main databases: a missing persons database in which families or law enforcement may enter information regarding missing persons and follow cases; an unidentified persons database where medical examiners and coroners may enter information on unidentified persons and the general public can search; and an unclaimed persons database for persons who have been identified but where family has not been found. The missing and unidentified person's databases interact to match information when entered into either system. As of October 2014, NamUs has resolved approximately 9000 cases of missing or unidentified persons.<sup id=\"rdp-ebb-cite_ref-NamUsHome_27-0\" class=\"reference\"><a href=\"#cite_note-NamUsHome-27\" rel=\"external_link\">[27]<\/a><\/sup>\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Shortcomings_of_existing_systems\">Shortcomings of existing systems<\/span><\/h2>\n<p>While all of the above systems and programs have been effective, they have common shortcomings. With the exception of death certificates, the entry of information into these disparate databases is voluntary on the part of medical examiners and coroners. Much of the data entry is manual or semi-automated, requiring significant human effort to accomplish. These two factors complicated by the limited resources of many DI systems leads to partial participation, even when offices would prefer to contribute.\n<\/p><p>Despite the recognition that there need to be standards regarding what data are collected and how it is classified and organized in a DI database, little progress has been made on this front. The few electronic communications of information directly from forensic offices to outside agencies are in the form of customized reports. There is currently no communication standard that would allow information to flow freely to, from and between DI electronic information systems, even when they are provided by the same vendor. These issues hinder the ability of forensic pathologists to effectively transform the data they are collecting into actionable information that would better inform public health and public safety agencies.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"A_path_forward\">A path forward<\/span><\/h2>\n<p>A prerequisite for improving the current situation is recognition in the forensic pathology community of the value of their data beyond the individual case. The examples of the government-based data sharing programs described above support the opinion that it is unlikely the federal government will solve the overarching problem of data consistency and analysis in forensic pathology. DI organizations, such as the National Association of Medical Examiners (NAME) and the International Association of Coroners and Medical Examiners (IACME), need to take leadership of this issue. Both of these professional organizations are dedicated to advancing DI and have existing standards for accreditation of offices.<sup id=\"rdp-ebb-cite_ref-NAMEHome_28-0\" class=\"reference\"><a href=\"#cite_note-NAMEHome-28\" rel=\"external_link\">[28]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-IACMEHome_29-0\" class=\"reference\"><a href=\"#cite_note-IACMEHome-29\" rel=\"external_link\">[29]<\/a><\/sup> While these groups are experts in the area of DI, they lack the necessary informatics expertise that will ensure success.\n<\/p><p>The Association for Pathology Informatics (API), a professional organization of pathologists with expertise in informatics, is the obvious partner for this endeavor. API's focus on data standards in pathology and the informatics education of pathologists complements the focus on standards and education by NAME and IACME for forensic pathology and DI. API has a history of reaching out to collaborate with other professional organizations in pathology and CI, and already works with government and industry groups in the development of data and communication standards.<sup id=\"rdp-ebb-cite_ref-APIHome_30-0\" class=\"reference\"><a href=\"#cite_note-APIHome-30\" rel=\"external_link\">[30]<\/a><\/sup>\n<\/p><p>Collaboration between these groups could address the challenges of sharing, merging and analyzing data from the large number of DI systems, each with their unique methods of organizing their data. Rather than attempt to start with a comprehensive solution, it may be advantageous to choose a handful of smaller projects to demonstrate value and to work through any issues that might become apparent. Data fields that are more likely to be consistent across different DI offices, such as basic demographics, cause of death and manner of death, are an obvious first step in this process. Toxicology and other laboratory results may be another potential \"low hanging fruit\" for collection and analysis. With some early successes, it will be easier to sit down and develop a more comprehensive solution, which should also include standards for the next generation of DI information systems.\n<\/p><p>The key is to develop a process by which data can be automatically transferred through an electronic interface from the individual DI office systems into a single database and subsequently back out to other systems for analysis. This includes several challenges that need to be addressed. Data fields in different systems may have different names, data types and conventions for expressing the data. For example, a field for manner of death may not only be named differently in different systems, but might be expressed as free text fields, defined text fields, abbreviations or even a numerical or symbolic representation for each manner of death. While it may seem like an insurmountable problem, the development of data standards has been accomplished in other areas of health care and is attainable for forensic pathology.<sup id=\"rdp-ebb-cite_ref-ShortliffeBio14_31-0\" class=\"reference\"><a href=\"#cite_note-ShortliffeBio14-31\" rel=\"external_link\">[31]<\/a><\/sup> A communication standard for transmitting the data would also need to be selected or developed. A communication standard ensures that the receiving system understands the message from the sending system and can place the communicated data into the proper fields. One commonly used an example for health care is Health Level 7. Another major issue to address is the security of the data, especially given the sensitive nature of this subset of personal health information.\n<\/p><p>Once this data are collected, policies regarding storage and access to the data for analysis and study will need to be created. There are currently many examples of secure data storage \"in the cloud\" that could be utilized. Some of this data can have great value if freely accessible on the web. NamUS is an excellent example of the power of open information. NVDRS has a mixture of data that is freely accessible or restricted based on whether the data may lead to disclosure of the identity of victims or suspects, and may serve as a guideline. Another issue to consider is the needs of law enforcement to restrict access to data for cases that are actively being investigated.\n<\/p><p>In addition to the expertise of forensic pathologists and pathology informaticians, this effort would require significant financial support, including; travel for forensic and informatics subject matter experts to design the project and define the standards, creation and support for the database, storage costs for the data, design of mechanisms to access or transfer the data for study, and general ongoing support for the project. Given the value of this data to many different government agencies and departments, it is reasonable to pursue funding through these agencies. It should be understood that the control over the collected data would reside with the professional organizations and not with the government itself since the subject matter experts are the best custodians of the data.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>Forensic pathology contains a wealth of information that is invaluable for many purposes. The current spectrum of information systems available to medical examiners and coroners are woefully inadequate to support the efficient use of this data. Data standards for DI and forensic information systems need to be developed. Standard communication protocols would enable the efficient automatic transfer of this data directly from medical examiner and coroner offices to national programs such as NVDRS and NamUs, to other public health, public safety and homeland security surveillance systems, and increase the timeliness and usability of this information. Clinical\/PI needs to collaborate with forensic pathology to create systems to better utilize DI data to protect the public health and safety.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Additional_info\">Additional info<\/span><\/h2>\n<p>Source of Support: None<br \/>\nConflict of Interest: None\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<ol class=\"references\">\n<li id=\"cite_note-ACGMEProg14-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-ACGMEProg14_1-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Accreditation Council for Graduate Medical Education (03 February 2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.acgme.org\/acgmeweb\/Portals\/0\/PFAssets\/ProgramRequirements\/381_clinical_informatics_02032014.pdf\" target=\"_blank\">\"ACGME Program Requirements for Graduate Medical Education in Clinical Informatics\"<\/a> (PDF)<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.acgme.org\/acgmeweb\/Portals\/0\/PFAssets\/ProgramRequirements\/381_clinical_informatics_02032014.pdf\" target=\"_blank\">http:\/\/www.acgme.org\/acgmeweb\/Portals\/0\/PFAssets\/ProgramRequirements\/381_clinical_informatics_02032014.pdf<\/a><\/span><span class=\"reference-accessdate\">. 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(2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3445301\" target=\"_blank\">\"A core curriculum for clinical fellowship training in pathology informatics\"<\/a>. <i>Journal of Pathology Informatics<\/i> <b>3<\/b>: 31. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2F2153-3539.100364\" target=\"_blank\">10.4103\/2153-3539.100364<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3445301\/\" target=\"_blank\">PMC3445301<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23024890\" target=\"_blank\">23024890<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3445301\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3445301<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+core+curriculum+for+clinical+fellowship+training+in+pathology+informatics&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=McClintock%2C+D.S.%3B+Levy%2C+B.P.%3B+Lane%2C+W.J.+et+al.&rft.au=McClintock%2C+D.S.%3B+Levy%2C+B.P.%3B+Lane%2C+W.J.+et+al.&rft.date=2012&rft.volume=3&rft.pages=31&rft_id=info:doi\/10.4103%2F2153-3539.100364&rft_id=info:pmc\/PMC3445301&rft_id=info:pmid\/23024890&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC3445301&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-YasnoffPublic00-4\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-YasnoffPublic00_4-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Yasnoff, W.A.; O\u2032Carroll, P.W.; Koo, D.; Linkins, R.W.; Kilbourne, E.M. (2000). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.lww.com\/jphmp\/Fulltext\/2000\/06060\/Public_Health_Informatics__Improving_and.10.aspx\" target=\"_blank\">\"Public health informatics: Improving and transforming public health in the information age\"<\/a>. <i>Journal of Public Health Management and Practice<\/i> <b>6<\/b> (6): 67\u201375<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.lww.com\/jphmp\/Fulltext\/2000\/06060\/Public_Health_Informatics__Improving_and.10.aspx\" target=\"_blank\">http:\/\/journals.lww.com\/jphmp\/Fulltext\/2000\/06060\/Public_Health_Informatics__Improving_and.10.aspx<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Public+health+informatics%3A+Improving+and+transforming+public+health+in+the+information+age&rft.jtitle=Journal+of+Public+Health+Management+and+Practice&rft.aulast=Yasnoff%2C+W.A.%3B+O%E2%80%B2Carroll%2C+P.W.%3B+Koo%2C+D.%3B+Linkins%2C+R.W.%3B+Kilbourne%2C+E.M.&rft.au=Yasnoff%2C+W.A.%3B+O%E2%80%B2Carroll%2C+P.W.%3B+Koo%2C+D.%3B+Linkins%2C+R.W.%3B+Kilbourne%2C+E.M.&rft.date=2000&rft.volume=6&rft.issue=6&rft.pages=67%E2%80%9375&rft_id=http%3A%2F%2Fjournals.lww.com%2Fjphmp%2FFulltext%2F2000%2F06060%2FPublic_Health_Informatics__Improving_and.10.aspx&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-MagnusonPublic14-5\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-MagnusonPublic14_5-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Magnuson, J.A.; O\u2019Carroll, P.W. (2014). \"Introduction to public health informatics\". In Magnuson, J.A.; Fu Jr., P.C.. <i>Public Health Informatics and Information Systems<\/i>. pp. 3-18. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-1-4471-4237-9_1\" target=\"_blank\">10.1007\/978-1-4471-4237-9_1<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" target=\"_blank\">ISBN<\/a> 9781447142379.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Introduction+to+public+health+informatics&rft.atitle=Public+Health+Informatics+and+Information+Systems&rft.aulast=Magnuson%2C+J.A.%3B+O%E2%80%99Carroll%2C+P.W.&rft.au=Magnuson%2C+J.A.%3B+O%E2%80%99Carroll%2C+P.W.&rft.date=2014&rft.pages=pp.%26nbsp%3B3-18&rft_id=info:doi\/10.1007%2F978-1-4471-4237-9_1&rft.isbn=9781447142379&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SpitzHist06-6\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-SpitzHist06_6-0\" rel=\"external_link\">6.0<\/a><\/sup> <sup><a href=\"#cite_ref-SpitzHist06_6-1\" rel=\"external_link\">6.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Spitz, D.J. 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In Spitz, W.U.; Spitz, D.J.. <i>Spitz and Fisher's Medicolegal Investigation of Death: Guidelines for the Application of Pathology to Crime Investigation<\/i>. pp. 3-21. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" target=\"_blank\">ISBN<\/a> 9780398075446<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/books.google.com\/books?id=-m_fb580Vx0C\" target=\"_blank\">https:\/\/books.google.com\/books?id=-m_fb580Vx0C<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=History+and+development+of+forensic+medicine+and+pathology&rft.atitle=Spitz+and+Fisher%27s+Medicolegal+Investigation+of+Death%3A+Guidelines+for+the+Application+of+Pathology+to+Crime+Investigation&rft.aulast=Spitz%2C+D.J.&rft.au=Spitz%2C+D.J.&rft.date=2006&rft.pages=pp.%26nbsp%3B3-21&rft.isbn=9780398075446&rft_id=https%3A%2F%2Fbooks.google.com%2Fbooks%3Fid%3D-m_fb580Vx0C&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-DOJANat13-7\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-DOJANat13_7-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">U.S. Department of Justice Office on Violence Against Women (April 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ncjrs.gov\/pdffiles1\/ovw\/241903.pdf\" target=\"_blank\">\"A National Protocol for Sexual Assault Medical Forensic Examinations\"<\/a> (PDF). U.S. Department of Justice<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ncjrs.gov\/pdffiles1\/ovw\/241903.pdf\" target=\"_blank\">https:\/\/www.ncjrs.gov\/pdffiles1\/ovw\/241903.pdf<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 30 December 2014<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=A+National+Protocol+for+Sexual+Assault+Medical+Forensic+Examinations&rft.atitle=&rft.aulast=U.S.+Department+of+Justice+Office+on+Violence+Against+Women&rft.au=U.S.+Department+of+Justice+Office+on+Violence+Against+Women&rft.date=April+2013&rft.pub=U.S.+Department+of+Justice&rft_id=https%3A%2F%2Fwww.ncjrs.gov%2Fpdffiles1%2Fovw%2F241903.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LevyImp13-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-LevyImp13_8-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Levy, B.P. (2013). \"Implementation and user satisfaction with forensic laboratory information systems in death investigation offices\". <i>The American Journal of Forensic Medicine and Pathology<\/i> <b>34<\/b> (1): 63\u201367. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1097%2FPAF.0b013e31827ab5c6\" target=\"_blank\">10.1097\/PAF.0b013e31827ab5c6<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23361076\" target=\"_blank\">23361076<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Implementation+and+user+satisfaction+with+forensic+laboratory+information+systems+in+death+investigation+offices&rft.jtitle=The+American+Journal+of+Forensic+Medicine+and+Pathology&rft.aulast=Levy%2C+B.P.&rft.au=Levy%2C+B.P.&rft.date=2013&rft.volume=34&rft.issue=1&rft.pages=63%E2%80%9367&rft_id=info:doi\/10.1097%2FPAF.0b013e31827ab5c6&rft_id=info:pmid\/23361076&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-DOJMed07-9\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-DOJMed07_9-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">U.S. Department of Justice Office of Justice Programs (June 2007). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.bjs.gov\/content\/pub\/pdf\/meco04.pdf\" target=\"_blank\">\"Medical Examiners and Coroners' Offices, 2004\"<\/a> (PDF). U.S. Department of Justice<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.bjs.gov\/content\/pub\/pdf\/meco04.pdf\" target=\"_blank\">http:\/\/www.bjs.gov\/content\/pub\/pdf\/meco04.pdf<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 30 December 2014<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Medical+Examiners+and+Coroners%27+Offices%2C+2004&rft.atitle=&rft.aulast=U.S.+Department+of+Justice+Office+of+Justice+Programs&rft.au=U.S.+Department+of+Justice+Office+of+Justice+Programs&rft.date=June+2007&rft.pub=U.S.+Department+of+Justice&rft_id=http%3A%2F%2Fwww.bjs.gov%2Fcontent%2Fpub%2Fpdf%2Fmeco04.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-CommitteeMed09-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-CommitteeMed09_10-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Committee on Identifying the Needs of the Forensic Sciences Community (2009). \"Medical examiner and coroner systems: Current and future needs\". In National Research Council of the National Academies. <i>Strengthening Forensic Science in the United States: <\/i>\nA Path Forward<i>. pp. 241\u2013268. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.17226%2F12589\" target=\"_blank\">10.17226\/12589<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" target=\"_blank\">ISBN<\/a> 9780309131308.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Medical+examiner+and+coroner+systems%3A+Current+and+future+needs&rft.atitle=Strengthening+Forensic+Science+in+the+United+States%3A+%0AA+Path+Forward&rft.aulast=Committee+on+Identifying+the+Needs+of+the+Forensic+Sciences+Community&rft.au=Committee+on+Identifying+the+Needs+of+the+Forensic+Sciences+Community&rft.date=2009&rft.pages=pp.%26nbsp%3B241%E2%80%93268&rft_id=info:doi\/10.17226%2F12589&rft.isbn=9780309131308&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span><\/i>\n<\/li>\n<li id=\"cite_note-ThompsonTheReal11-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-ThompsonTheReal11_11-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Thompson, A.C.; Secret, M.; Bergman, L.; Bartlett S. (31 January 2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.propublica.org\/article\/the-real-csi-americas-patchwork-system-of-death-investigation\" target=\"_blank\">\"The Real \u2018CSI\u2019: How America\u2019s Patchwork System of Death Investigations Puts the Living at Risk\"<\/a>. <i>Pro Publica<\/i>. Pro Publica, Inc<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.propublica.org\/article\/the-real-csi-americas-patchwork-system-of-death-investigation\" target=\"_blank\">http:\/\/www.propublica.org\/article\/the-real-csi-americas-patchwork-system-of-death-investigation<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 30 December 2014<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=The+Real+%E2%80%98CSI%E2%80%99%3A+How+America%E2%80%99s+Patchwork+System+of+Death+Investigations+Puts+the+Living+at+Risk&rft.atitle=Pro+Publica&rft.aulast=Thompson%2C+A.C.%3B+Secret%2C+M.%3B+Bergman%2C+L.%3B+Bartlett+S.&rft.au=Thompson%2C+A.C.%3B+Secret%2C+M.%3B+Bergman%2C+L.%3B+Bartlett+S.&rft.date=31+January+2011&rft.pub=Pro+Publica%2C+Inc&rft_id=http%3A%2F%2Fwww.propublica.org%2Farticle%2Fthe-real-csi-americas-patchwork-system-of-death-investigation&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-CambridgeTheAcc10-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-CambridgeTheAcc10_12-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Cambridge, B.; Cina, S.J. (2010). \"The accuracy of death certificate completion in a suburban community\". <i>The American Journal of Forensic Medicine and Pathology<\/i> <b>31<\/b> (3): 232\u2013235. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1097%2FPAF.0b013e3181e5e0e2\" target=\"_blank\">10.1097\/PAF.0b013e3181e5e0e2<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20512028\" target=\"_blank\">20512028<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+accuracy+of+death+certificate+completion+in+a+suburban+community&rft.jtitle=The+American+Journal+of+Forensic+Medicine+and+Pathology&rft.aulast=Cambridge%2C+B.%3B+Cina%2C+S.J.&rft.au=Cambridge%2C+B.%3B+Cina%2C+S.J.&rft.date=2010&rft.volume=31&rft.issue=3&rft.pages=232%E2%80%93235&rft_id=info:doi\/10.1097%2FPAF.0b013e3181e5e0e2&rft_id=info:pmid\/20512028&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SnyderRed14-13\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SnyderRed14_13-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Snyder, M.L.; Love, S.A.; Sorlie, P.D. et al. (2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4113199\" target=\"_blank\">\"Redistribution of heart failure as the cause of death: the Atherosclerosis Risk in Communities Study\"<\/a>. <i>Population Health Metrics<\/i> <b>12<\/b> (1): 10. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1478-7954-12-10\" target=\"_blank\">10.1186\/1478-7954-12-10<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4113199\/\" target=\"_blank\">PMC4113199<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24716810\" target=\"_blank\">24716810<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4113199\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4113199<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Redistribution+of+heart+failure+as+the+cause+of+death%3A+the+Atherosclerosis+Risk+in+Communities+Study&rft.jtitle=Population+Health+Metrics&rft.aulast=Snyder%2C+M.L.%3B+Love%2C+S.A.%3B+Sorlie%2C+P.D.+et+al.&rft.au=Snyder%2C+M.L.%3B+Love%2C+S.A.%3B+Sorlie%2C+P.D.+et+al.&rft.date=2014&rft.volume=12&rft.issue=1&rft.pages=10&rft_id=info:doi\/10.1186%2F1478-7954-12-10&rft_id=info:pmc\/PMC4113199&rft_id=info:pmid\/24716810&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC4113199&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-GermanTheAcc11-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-GermanTheAcc11_14-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">German, R.R.; Fink, A.K.; Heron, M. et al. (2011). \"The accuracy of cancer mortality statistics based on death certificates in the United States\". <i>Population Health Metrics<\/i> <b>35<\/b> (2): 126\u2013131. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.canep.2010.09.005\" target=\"_blank\">10.1016\/j.canep.2010.09.005<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20952269\" target=\"_blank\">20952269<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+accuracy+of+cancer+mortality+statistics+based+on+death+certificates+in+the+United+States&rft.jtitle=Population+Health+Metrics&rft.aulast=German%2C+R.R.%3B+Fink%2C+A.K.%3B+Heron%2C+M.+et+al.&rft.au=German%2C+R.R.%3B+Fink%2C+A.K.%3B+Heron%2C+M.+et+al.&rft.date=2011&rft.volume=35&rft.issue=2&rft.pages=126%E2%80%93131&rft_id=info:doi\/10.1016%2Fj.canep.2010.09.005&rft_id=info:pmid\/20952269&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-ParrishAss95-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-ParrishAss95_15-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Parrish, Gib (1995). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.cdc.gov\/nchs\/data\/ice\/ice95v1\/ice_i.pdf\" target=\"_blank\">\"Assessing and improving the quality of data from medical examiners and coroners\"<\/a>. 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International Association of Coroners and Medical Examiners<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.theiacme.com\/\" target=\"_blank\">http:\/\/www.theiacme.com\/<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 01 April 2015<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=International+Association+of+Coroners+and+Medical+Examiners+-+Home&rft.atitle=&rft.pub=International+Association+of+Coroners+and+Medical+Examiners&rft_id=http%3A%2F%2Fwww.theiacme.com%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-APIHome-30\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-APIHome_30-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pathologyinformatics.org\/\" target=\"_blank\">\"Association for Pathology Informatics\"<\/a>. Association for Pathology Informatics<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pathologyinformatics.org\/\" target=\"_blank\">http:\/\/www.pathologyinformatics.org\/<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 01 April 2015<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Association+for+Pathology+Informatics&rft.atitle=&rft.pub=Association+for+Pathology+Informatics&rft_id=http%3A%2F%2Fwww.pathologyinformatics.org%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-ShortliffeBio14-31\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-ShortliffeBio14_31-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Hammond, W.E.; Jaffe, C.; Cimino, J.J.; Huff, S.M. (2014). \"Standards in biomedical informatics\". In Shortliffe, E.H.; Cimino, J.J.. <i>Biomedical Informatics: Computer Applications in Health Care and Biomedicine<\/i>. pp. 211\u2013253. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-1-4471-4474-8\" target=\"_blank\">10.1007\/978-1-4471-4474-8<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" target=\"_blank\">ISBN<\/a> 9781447144731.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Standards+in+biomedical+informatics&rft.atitle=Biomedical+Informatics%3A+Computer+Applications+in+Health+Care+and+Biomedicine&rft.aulast=Hammond%2C+W.E.%3B+Jaffe%2C+C.%3B+Cimino%2C+J.J.%3B+Huff%2C+S.M.&rft.au=Hammond%2C+W.E.%3B+Jaffe%2C+C.%3B+Cimino%2C+J.J.%3B+Huff%2C+S.M.&rft.date=2014&rft.pages=pp.%26nbsp%3B211%E2%80%93253&rft_id=info:doi\/10.1007%2F978-1-4471-4474-8&rft.isbn=9781447144731&rfr_id=info:sid\/en.wikipedia.org:Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192209\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.693 seconds\nReal time usage: 0.714 seconds\nPreprocessor visited node count: 23474\/1000000\nPreprocessor generated node count: 36640\/1000000\nPost\u2010expand include size: 177624\/2097152 bytes\nTemplate argument size: 65007\/2097152 bytes\nHighest expansion depth: 18\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 695.460 1 - -total\n 86.97% 604.826 1 - Template:Reflist\n 75.80% 527.174 31 - Template:Citation\/core\n 42.95% 298.726 16 - Template:Cite_journal\n 23.57% 163.888 10 - Template:Cite_web\n 14.27% 99.227 5 - Template:Cite_book\n 8.82% 61.345 1 - Template:Infobox_journal_article\n 8.51% 59.175 1 - Template:Infobox\n 5.99% 41.663 31 - Template:Citation\/identifier\n 5.15% 35.815 80 - Template:Infobox\/row\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:7944-0!*!0!!en!*!* and timestamp 20181214192209 and revision id 24848\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation\">https:\/\/www.limswiki.org\/index.php\/Journal:The_need_for_informatics_to_support_forensic_pathology_and_death_investigation<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","4eab7c6abfe5289f728109669eaa90ed_images":[],"4eab7c6abfe5289f728109669eaa90ed_timestamp":1544815329,"8b00807d95773df324df7278fa97c909_type":"article","8b00807d95773df324df7278fa97c909_title":"The development of the Public Health Research Data Management System (van Gaans et al. 2015)","8b00807d95773df324df7278fa97c909_url":"https:\/\/www.limswiki.org\/index.php\/Journal:The_development_of_the_Public_Health_Research_Data_Management_System","8b00807d95773df324df7278fa97c909_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:The development of the Public Health Research Data Management System\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nThe development of the Public Health Research Data Management SystemJournal\n \nelectronic Journal of Health InformaticsAuthor(s)\n \nvan Gaans, Deborah; D'Onise, Katina; Cardone, Tony; McDermott, RobynAuthor affiliation(s)\n \nUniversity of South Australia, James Cook UniversityPrimary contact\n \nEmail: deborah.vangaans@unisa.edu.au; Tel: +618 830 22908Year published\n \n2015Volume and issue\n \n9(1)Page(s)\n \ne10DOI\n \nNoneISSN\n \n1446-4381Distribution license\n \nCreative Commons Attribution-NonCommercial-ShareAlike 3.0 AustraliaWebsite\n \nhttp:\/\/www.ejhi.net\/ojs\/index.php\/ejhi\/article\/view\/301\/186Download\n \nhttp:\/\/www.ejhi.net\/ojs\/index.php\/ejhi\/article\/download\/301\/186 (PDF)\n\nContents\n\n1 Abstract \n2 Introduction \n3 Methods \n4 Results \n\n4.1 Design \n4.2 Access \n\n\n5 Conclusion \n6 Acknowledgements \n7 Conflicts of interest \n8 Correspondence \n9 References \n10 Notes \n\n\n\nAbstract \nThe design and development of the Public Health Research Data Management System highlights how it is possible to construct an information system, which allows greater access to well, preserved public health research data to enable it to be reused and shared. The Public Health Research Data Management System (PHRDMS) manages clinical, health service, community and survey research data within a secure web environment. The conceptual model under pinning the PHRDMS is based on three main entities: participant, community and health service. The PHRDMS was designed to provide data management to allow for data sharing and reuse. The system has been designed to enable rigorous research and ensure that: data that are unmanaged be managed, data that are disconnected be connected, data that are invisible be findable, data that are single use be reusable, within a structured collection. The PHRDMS is currently used by researchers to answer a broad range of policy relevant questions, including monitoring incidence of renal disease, cardiovascular disease, diabetes and mental health problems in different risk groups.\nKeywords: Public Health; Modelling; Database Management Systems; Secondary Use\n\nIntroduction \nEpidemiological and health related statistical information provide the evidence base for health care and policy, by providing accurate and reliable data including the health of minority and vulnerable populations.[1] However, in public health research, data management is the poor cousin of analysis, as it is often undervalued and underfunded.[2] Without accurate data there is little capacity to monitor changes in health status, to evaluate access to services and the response of services to needs, or to quantify the resources expended on health services and programs.[1]\nManaging the life cycle of scientific data presents many challenges including deciding responsibilities, funding, resource allocation, what data should be kept and for how long.[3] Research data is a valuable asset and while data management is a necessary part of good research it is not always undertaken well by the researcher. Ackerman and Osborne (2005)[4] highlight the importance of an integrated system for managing health research data to ensure the smooth transfer of data from the hospital\u2019s patient record database to the research database, and finally to statistical software for analysis.\nIn a system that emphasizes competition rather than collaboration among researchers, data sets resulting from multimillion dollar investments from tax payers sit idle inside locked computers, only available to a small number of researchers despite their containing the seeds that would allow for the exploration of a vast number of important research questions that could change the healthcare landscape.[5] There are indications that public and foundation funders of public health research wish to strengthen data sharing policies, shepherding epidemiologists down the road already travelled by geneticists.[2] Secondary research refers to the use of research data to study a problem that was not the focus of the original data collection.[6] This secondary analysis may involve the combination of one data set with another, address new questions or use new analytical methods for evaluation.[6] The benefits of data sharing are many and include:\n\n Allowing, the same data to be used to answer new questions that may be relevant far beyond the original study.[2]\n Accelerating investigations already under way and taking advantage of past investments in science.[3]\n Obtaining a statistically meaningful number of cases quicker than studies in a single centre, so the applied research results can be used quicker as well and particularly for rare diseases a critical mass of cases can be obtained in sufficient quality that no single institution could obtain.[7]\n Generates opportunities for additional publications through collaboration, and may increase the citation rate of primary publications.[8]\n Once investments in infrastructure have been made, recycling and combining data provide access to maximum knowledge for minimal additional cost.[2]\n Sharing data increases the visibility and relevance of research output.[8]\n Being able to extend the study dataset through linking to other data sources has the potential to enable the important research questions for the study to be better answered, with the added benefit of generally reducing the burden on respondents.[9]\nTo enable reuse, data must be well preserved. Community standards for data description and exchange are crucial as these facilitate data reuse by making it easier to import, export, compare, combine and understand data.[3] As Pisani (2010)[2] states improved documentation will lead to data being combined more easily across time, locations and sources.\nThe development of public health information systems requires an understanding of the principles, practices, structures and settings in which these systems operate.[10] Issues of conflicting data standards, the need for interoperable tools for exchanging and sharing data and the need for innovative solutions to address integrated disease surveillance, among many other issues, are driving forces to formalize design strategies in public health information.[10] Details regarding the specific design and features of such databases are not readily available in the literature and yet, this type of practical information would be valuable for clinicians and researchers who wish to design database systems tailored to their particular requirements.[4]\n\nMethods \nThe conceptualization of the Public Health Data Management System (PHRDMS) occurred through a series of consultative meetings between public health researchers, information technology business intelligence specialists and data managers. The Public Health Data Management System (PHRDMS) stores data, metadata and documents that are generated throughout the lifecycle of research projects. The PHRDMS provides a structure to allow research data to be maintained in accordance with a large number of laws, regulations and conventions, and was designed specifically to meet the standards of: University of South Australia, (2012) UniSA Framework for the Responsible Conduct of Research[11], James Cook University, (2012) Code of Conduct[12], and National Health and Medical Research Council, (2007) Australian Code for the Responsible Conduct of Research. [13] The guidelines were synthesised into the following core set, that have underpinned the development of the PHRDMS:\n\n Researchers should retain research data and primary materials for sufficient time to allow reference to them by other researchers and interested parties. For published research data, this may be for as long as interest and discussion persist following publication. \n When considering how long research data and primary materials are to be retained, the researcher must take account of professional standards, legal requirements and contractual arrangements. \n Research data should be made available for use by other researchers unless this is prevented by ethical, privacy or confidentiality matters. \n Research data should be retained for at least the minimum period specified in the institutional policy. \n The institutional policy on the secure and safe disposal of primary materials and research data must be followed (note that for patient records these are to be kept indefinitely).\n Researchers must manage research data and primary materials in accordance with the policy of the institution. \n Sufficient materials and data are retained to justify the outcomes of the research and to defend them if they are challenged. That security and confidentiality of the data is undertaken and maintained. \n Keep clear and accurate records of the research methods and data sources, including any approvals granted, during and after the research process. \n Ensure that research data and primary materials are kept in safe and secure storage provided, even when not in current use. \n Provide the same level of care and protection to primary research records, such as laboratory notebooks, as to the analysed research data. \n Retain research data, including electronic data, in a durable, indexed and retrievable form. \n Maintain a catalogue of research data in an accessible form. \n Manage research data and primary materials according to ethical protocols and relevant legislation. \n Maintain confidentiality of research data and primary materials. Researchers given access to confidential information must maintain that confidentiality. \n Primary materials and confidential research data must be kept in secure storage. Confidential information must only be used in ways agreed with those who provided it. Particular care must be exercised when confidential data are made available for discussion.\n\r\n\nThe PHRDMS was constructed by the Information Strategy and Technology Services Unit within the University of South Australia through consultation with population health researchers. During the design phase of the PHRDMS, specific researcher requirements were identified, these included:\n\n Ensure data is accessible to who need it: including remote regions, different universities.\n Easily used by researchers as it fits with their business process Eg. Data entry forms look like the questionnaire.\n Ability to deidentify \/ reidentify participants if necessary.\n Ability to link data from other sources.\n Ability to create reports for: individual participants, communities, health services, projects.\n Allow for version control of project documents and derived datasets.\n Data fits with International\/ national standards where possible.\n Temporal view of data.\n Logging of data extracts.\n Formal process of data upload and extraction.\n Metadata development, cleaning, maintenance.\n Developing and implementing protocols regarding storage, retrieval, security and integrity of the data to be used by key stakeholders. \nResults \nAll of the data, metadata and documents that form part of any public health research project are captured within the PHRDMS. As can be seen in Figure 1 this includes ethics agreements, reports, questionnaires, methods, approvals, publications, data dictionary, and study protocols. \n\n\n\n\n\n\n\n\n\n Figure 1. Data, Metadata and Documents that are captured within the Public Health Research Data Management System\n\n\n\nA copy of the plain language statement for each research project, as required by ethical standards of research, is held within the PHRDM System as a .pdf file. Participant consent agreements are stored as a .pdf file for each project participant within the PHRDM System. Through the security structure of the PHRDM System research participants are deidentified however the system also has the capability to make data reidentifiable (to system administrator roles only) so that reports can be sent to individual participants, participants can be contacted for further involvement in research projects, and also for data linkage purposes. \nThe participant\u2019s consent agreements often have a series of statements relating to particular data \/ information and the participant can choose to consent to the individual statements. These statements often reflect being contacted for further research projects, having the participants data forwarded on to their primary health care clinic etc. These statements are captured with the participants consent within the PHRDM System, so that the agreement between the participant and the project can be maintained during data extraction and reporting. The research projects often have agreements with Communities, Primary Health Care Clinics, hospitals, data custodians etc. Copies of these agreements are held as .pdfs within the PHRDM System for each research project. \nOne of the added features of the PHRDMS is that it also maintains an audit trail and history of all data modifications. The audit trail begins from the time the data has been entered into the system and all modifications to the data are recorded in audit tables which are maintained as part of the system. The audit tables are a log of the change that has been made to the data, at what time and by who. Data that has been manually entered into the database can be corrected through the data entry screens and bulk uploaded data will be backed out of the PHRDM system and then reloaded. \nAll surveys\/ questionnaires that are used within a research project undergo an ethics approval process before they are administered. Sometimes a single survey\/questionnaire will undergo a number of revisions. All versions of the surveys\/questionnaires that have been used within the research project are maintained within the PHRDM System. \nThe PHRDMS stores demographic, vaccinations, diagnosed chronic conditions, medications, lifestyle measures, pathology results, mental health, management plans, allied health and specialist referrals, gestational data and child data. The system allows the system administrator to add clinical variables as needed by the research project, as well as surveys.\n\nDesign \nThe PHRDMS is a very flexible user friendly system. The data model that underlies the PHRDMS is based on three distinct entities and the relationships between them (Figure 2). This data model allows users to customise their view of the database to the variables that they are collecting for their own research project. Users can therefore add new variables to the participant, community, or Primary Health Care Centre entity. The system also allows new questions and answers from questionnaires to be added. The PHRDMS does not store derived variables, only raw data, which allows the users to classify the data according to individual researcher requirements.\n\n\n\n\n\n\n\n\n\n Figure 2. The Entities within the Public Health Research Data Management System\n\n\n\nThe PHRDM System produces a number of standard research reports and individual clinical variables can be extracted into an excel spreadsheet. The system also allows codes to be assigned to data so that it can be used directly within Stata[13] once it has been extracted from the system. The system also produces a log report to capture the history of changes made to the data within the system due to data corrections. All data extracts are recorded within the PHRDMS to maintain a history of what data was extracted by who, at what time, for what purpose. \nThe PHRDM system allows for data linkage to external data sets. Data from external data custodians is able to be linked to the participant, community, primary health care centre, or the participant\u2019s pathology result. The data is initially held in a staging area while it is reviewed against the current set of data variable rules. Any external data that does not match the existing data variable rules is able to be reviewed by the system administrator and either be corrected (in the case of a data error) or rejected from the data upload. The data upload and cleansing process is captured within the PHRDMS to maintain an activity log for administration purposes. \nDue to the nature of Public Health research many of the projects contained within the PHRDMS collect the same clinical variables and often administer the same questionnaires. The PHRDMS maintains projects separately but with many of the research staff working across numerous projects it is possible for data to be viewed as a total collection (Figure 3), allowing for variables from a number of projects to be reused to answer new research questions.\n\n\n\n\n\n\n\n\n\n Figure 3. The Relationship between projects within the Public Health Research Data Management System\n\n\n\nAccess \nInitial access to the database is provided through the Australian Access Federation, which will allow researchers into the database, who belong to institutions that are registered with the Australian Access Federation. Therefore allowing researchers access to the system anywhere they are able to get access to the internet. Researchers are then able to be granted access to project data for which they have signed project confidentiality agreements. Access to the project data is then governed by the role that is assigned by the system administrator. The PHRDMS manages data access through the following roles: System Administrator, Researcher, and Data Entry. Functionality within the database is applied to each role with all roles other than system administrator being applied to a specific project.\n\nConclusion \nThe Public Health Data Management System stores and manages a large cohort of Indigenous adults and children, both \u201cwell\u201d and who already have a chronic condition on study enrolment. The dataset will grow due to recruitment of participants over time and increase in scope as new datasets are linked to the cohort. The information generated from the system will be used for the immediate research aims of the Centre of Research Excellence in Prevention of Chronic Conditions and will be able to be used by researchers into the future to answer a much broader range of policy relevant questions, including monitoring incidence of renal, cardiovascular disease, diabetes and mental health problems in different risk groups. This cohort will include these participants at baseline, but also be able to identify incidence of disease in those free of problems at recruitment. \nThe design and development of the Public Health Research Data Management System highlights how it is possible to construct an information system which allows greater access to well preserved public health research data to enable it to be reused and shared. While the development of the PHRDMS has been based on Australian guidelines, the conceptual model under pinning the PHRDMS which is based on the three main entities: participant, community and health service could be used internationally.\n\nAcknowledgements \nThe research reported in this paper is a project of the Australian Primary Health Care Research Institute, which is supported by a grant from the Commonwealth of Australia as represented by the Department of Health. The information and opinions contained in it do not necessarily reflect the views or policy of the Australian Primary Health Care Research Institute or the Australian Government Department of Health.\n\nConflicts of interest \nNone declared.\n\nCorrespondence \nDr Deborah van Gaans (Corresponding Author)\r\n\nManager: Research Data\r\n\nCentre for Research Excellence in the Prevention of Chronic Conditions in Rural and Remote Populations\r\n\nSchool of Population Health, University of South Australia\r\n\nLevel 8, South Australian Health & Medical Research Institute (SAMHRI)\r\n\nNorth Terrace, Adelaide, 5001\r\n\nTel: +618 830 22908\r\n\ndeborah.vangaans@unisa.edu.au\r\n\nResearch Associate\r\n\nDept. of Geography, Environment and Population,\r\n\nThe University of Adelaide,\r\n\nNorth Terrace, Adelaide, South Australia, 5005\r\n\nDr Katina D\u2019Onise\r\n\nSenior Research Fellow\r\n\nCentre for Research Excellence in the Prevention of Chronic Conditions in Rural and Remote Populations\r\n\nSchool of Population Health, University of South Australia\r\n\nLevel 8, South Australian Health & Medical Research Institute (SAMHRI)\r\n\nNorth Terrace, Adelaide, 5001\r\n\nTel: +618 830 21221\r\n\nkatina.d\u2019onise@unisa.edu.au\r\n\nMr. Tony Cardone\r\n\nBusiness Intelligence Specialist\r\n\nChancellery,\r\n\nBusiness Intelligence and Planning, University of South Australia\r\n\nCity West Campus\r\n\nNorth Terrace, Adelaide, 5001\r\n\nTel: +618 830 27286\r\n\ntony.cardone@unisa.edu.au\r\n\nProf Robyn McDermott\r\n\nProfessor of Public Health Medicine\r\n\nCollege of Public Health, Medical and Veterinary Sciences\r\n\nJames Cook University, PO Box 6811, Cairns QLD\r\n\n4870 Australia\r\n\nTel (07) 4232 1575\r\n\nrobyn.mcdermott@jcu.edu.au\r\n\n\nReferences \n\n\n\u2191 1.0 1.1 Thompson, S.C.; Woods, J.A.; Katzenellenbogen, J.M. (2012). \"The quality of indigenous identification in administrative health data in Australia: Insights from studies using data linkage\". BMC Medical Informatics and Decision Making 12: 133. doi:10.1186\/1472-6947-12-133. PMC PMC3536611. PMID 23157943. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3536611 .   \n\n\u2191 2.0 2.1 2.2 2.3 2.4 Pisani, E.; AbouZahr, C.. \"Sharing health data: Good intentions are not enough\". Bulletin of the World Health Organization 88 (6): 462\u2013466. doi:10.2471\/BLT.09.074393. PMC PMC2878150. PMID 20539861. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2878150 .   \n\n\u2191 3.0 3.1 3.2 Lynch, C.. \"Big data: How do your data grow?\". Nature 455 (7209): 28\u201329. doi:10.1038\/455028a. PMID 18769419.   \n\n\u2191 4.0 4.1 Ackerman, I.N.; Osborne, R.H.. \"Integrating data to facilitate clinical research: A case study\". Informatics in Primary Care 13 (4): 263\u2013270. PMID 16510023.   \n\n\u2191 Carvalho, E.C.; Batilana, A.P.; Simkins, J. et al.. \"Application description and policy model in collaborative environment for sharing of information on epidemiological and clinical research data sets\". PLoS One 5 (2): e9314. doi:10.1371\/journal.pone.0009314. PMC PMC2824801. PMID 20174560. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2824801 .   \n\n\u2191 6.0 6.1 Law, Margaret. [http:\/\/www.iassistdata.org\/iq\/reduce-reuse-recycle-issues-secondary-use-research-data \"Reduce, reuse, recycle: Issues\nin the secondary use of research data\"]. IASSIST Quarterly 29 (Spring): 5. http:\/\/www.iassistdata.org\/iq\/reduce-reuse-recycle-issues-secondary-use-research-data .   \n\n\u2191 Elger, B.S.; Iavindrasana, J.; Iacono, L.L. et al.. \"Strategies for health data exchange for secondary, cross-institutional clinical research\". Computer Methods and Programs in Biomedicine 99 (3): 230\u2013251. doi:10.1016\/j.cmpb.2009.12.001. PMID 20089327.   \n\n\u2191 8.0 8.1 Piwowar, H.A.; Becich, M.J.; Bilofsky, H.; Crowley, R.S.; caBIG Data Sharing and Intellectual Capital Workspace. \"Towards a data sharing culture: Recommendations for leadership from academic health centers\". PLoS Medicine 5 (9): e183. doi:10.1371\/journal.pmed.0050183. PMC PMC2528049. PMID 18767901. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2528049 .   \n\n\u2191 Soloff, C.; Sanson, A.; Wake, M.; Harrison, L.. \"Enhancing longitudinal studies by linkage to national databases: Growing Up in Australia, the longitudinal study of Australian children\". International Journal of Social Research Methodology 10 (5): 349\u2013363. doi:10.1080\/13645570701677060.   \n\n\u2191 10.0 10.1 Reeder, B.; Hills, R.A.; Demiris, G.; Revere, D.; Pina, J.. \"Reusable design: A proposed approach to public health informatics system design\". BMC Public Health 11: 116. doi:10.1186\/1471-2458-11-116. PMC PMC3053242. PMID 21333000. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3053242 .   \n\n\u2191 \"UniSA Framework for the Responsible Conduct of Research\". University of South Australia. 2012. http:\/\/w3.unisa.edu.au\/RES\/ethics\/integrity\/default.asp . Retrieved 26 November 2012 .   \n\n\u2191 \"Code of Conduct\". James Cook University. 2012. http:\/\/www.jcu.edu.au\/policy\/governance\/conduct\/JCUDEV_007161.html . Retrieved 26 November 2012 .   \n\n\u2191 13.0 13.1  (PDF) Australian Code for the Responsible Conduct of Research. National Health and Medical Research Council, Australian Government. 2007. ISBN 1864964383. https:\/\/www.nhmrc.gov.au\/_files_nhmrc\/publications\/attachments\/r39_australian_code_responsible_conduct_research_150107.pdf . Retrieved 26 November 2012 .   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. The figures have been moved around slightly to be closer to their reference in the text.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:The_development_of_the_Public_Health_Research_Data_Management_System\">https:\/\/www.limswiki.org\/index.php\/Journal:The_development_of_the_Public_Health_Research_Data_Management_System<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on public health informaticsLIMSwiki journal articles on software\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 12 February 2016, at 21:25.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 932 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","8b00807d95773df324df7278fa97c909_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_The_development_of_the_Public_Health_Research_Data_Management_System skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:The development of the Public Health Research Data Management System<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>The design and development of the Public Health Research Data Management System highlights how it is possible to construct an <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" target=\"_blank\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> system, which allows greater access to well, preserved public health research data to enable it to be reused and shared. The Public Health Research Data Management System (PHRDMS) manages clinical, health service, community and survey research data within a secure web environment. The conceptual model under pinning the PHRDMS is based on three main entities: participant, community and health service. The PHRDMS was designed to provide data management to allow for data sharing and reuse. The system has been designed to enable rigorous research and ensure that: data that are unmanaged be managed, data that are disconnected be connected, data that are invisible be findable, data that are single use be reusable, within a structured collection. The PHRDMS is currently used by researchers to answer a broad range of policy relevant questions, including monitoring incidence of renal disease, cardiovascular disease, diabetes and mental health problems in different risk groups.\n<\/p><p><b>Keywords:<\/b> Public Health; Modelling; Database Management Systems; Secondary Use\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>Epidemiological and health related statistical information provide the evidence base for health care and policy, by providing accurate and reliable data including the health of minority and vulnerable populations.<sup id=\"rdp-ebb-cite_ref-ThompsonTheQual12_1-0\" class=\"reference\"><a href=\"#cite_note-ThompsonTheQual12-1\" rel=\"external_link\">[1]<\/a><\/sup> However, in public health research, data management is the poor cousin of analysis, as it is often undervalued and underfunded.<sup id=\"rdp-ebb-cite_ref-PisaniSharing10_2-0\" class=\"reference\"><a href=\"#cite_note-PisaniSharing10-2\" rel=\"external_link\">[2]<\/a><\/sup> Without accurate data there is little capacity to monitor changes in health status, to evaluate access to services and the response of services to needs, or to quantify the resources expended on health services and programs.<sup id=\"rdp-ebb-cite_ref-ThompsonTheQual12_1-1\" class=\"reference\"><a href=\"#cite_note-ThompsonTheQual12-1\" rel=\"external_link\">[1]<\/a><\/sup>\n<\/p><p>Managing the life cycle of scientific data presents many challenges including deciding responsibilities, funding, resource allocation, what data should be kept and for how long.<sup id=\"rdp-ebb-cite_ref-LynchHow08_3-0\" class=\"reference\"><a href=\"#cite_note-LynchHow08-3\" rel=\"external_link\">[3]<\/a><\/sup> Research data is a valuable asset and while data management is a necessary part of good research it is not always undertaken well by the researcher. Ackerman and Osborne (2005)<sup id=\"rdp-ebb-cite_ref-AckermanInt05_4-0\" class=\"reference\"><a href=\"#cite_note-AckermanInt05-4\" rel=\"external_link\">[4]<\/a><\/sup> highlight the importance of an integrated system for managing health research data to ensure the smooth transfer of data from the <a href=\"https:\/\/www.limswiki.org\/index.php\/Hospital\" title=\"Hospital\" target=\"_blank\" class=\"wiki-link\" data-key=\"b8f070c66d8123fe91063594befebdff\">hospital<\/a>\u2019s patient record database to the research database, and finally to statistical software for analysis.\n<\/p><p>In a system that emphasizes competition rather than collaboration among researchers, data sets resulting from multimillion dollar investments from tax payers sit idle inside locked computers, only available to a small number of researchers despite their containing the seeds that would allow for the exploration of a vast number of important research questions that could change the healthcare landscape.<sup id=\"rdp-ebb-cite_ref-CarvalhoApp10_5-0\" class=\"reference\"><a href=\"#cite_note-CarvalhoApp10-5\" rel=\"external_link\">[5]<\/a><\/sup> There are indications that public and foundation funders of public health research wish to strengthen data sharing policies, shepherding epidemiologists down the road already travelled by geneticists.<sup id=\"rdp-ebb-cite_ref-PisaniSharing10_2-1\" class=\"reference\"><a href=\"#cite_note-PisaniSharing10-2\" rel=\"external_link\">[2]<\/a><\/sup> Secondary research refers to the use of research data to study a problem that was not the focus of the original data collection.<sup id=\"rdp-ebb-cite_ref-LawReduce05_6-0\" class=\"reference\"><a href=\"#cite_note-LawReduce05-6\" rel=\"external_link\">[6]<\/a><\/sup> This secondary analysis may involve the combination of one data set with another, address new questions or use new analytical methods for evaluation.<sup id=\"rdp-ebb-cite_ref-LawReduce05_6-1\" class=\"reference\"><a href=\"#cite_note-LawReduce05-6\" rel=\"external_link\">[6]<\/a><\/sup> The benefits of data sharing are many and include:\n<\/p>\n<ul><li> Allowing, the same data to be used to answer new questions that may be relevant far beyond the original study.<sup id=\"rdp-ebb-cite_ref-PisaniSharing10_2-2\" class=\"reference\"><a href=\"#cite_note-PisaniSharing10-2\" rel=\"external_link\">[2]<\/a><\/sup><\/li><\/ul>\n<ul><li> Accelerating investigations already under way and taking advantage of past investments in science.<sup id=\"rdp-ebb-cite_ref-LynchHow08_3-1\" class=\"reference\"><a href=\"#cite_note-LynchHow08-3\" rel=\"external_link\">[3]<\/a><\/sup><\/li><\/ul>\n<ul><li> Obtaining a statistically meaningful number of cases quicker than studies in a single centre, so the applied research results can be used quicker as well and particularly for rare diseases a critical mass of cases can be obtained in sufficient quality that no single institution could obtain.<sup id=\"rdp-ebb-cite_ref-ElgerStrat10_7-0\" class=\"reference\"><a href=\"#cite_note-ElgerStrat10-7\" rel=\"external_link\">[7]<\/a><\/sup><\/li><\/ul>\n<ul><li> Generates opportunities for additional publications through collaboration, and may increase the citation rate of primary publications.<sup id=\"rdp-ebb-cite_ref-PiwowarTowards08_8-0\" class=\"reference\"><a href=\"#cite_note-PiwowarTowards08-8\" rel=\"external_link\">[8]<\/a><\/sup><\/li><\/ul>\n<ul><li> Once investments in infrastructure have been made, recycling and combining data provide access to maximum knowledge for minimal additional cost.<sup id=\"rdp-ebb-cite_ref-PisaniSharing10_2-3\" class=\"reference\"><a href=\"#cite_note-PisaniSharing10-2\" rel=\"external_link\">[2]<\/a><\/sup><\/li><\/ul>\n<ul><li> Sharing data increases the visibility and relevance of research output.<sup id=\"rdp-ebb-cite_ref-PiwowarTowards08_8-1\" class=\"reference\"><a href=\"#cite_note-PiwowarTowards08-8\" rel=\"external_link\">[8]<\/a><\/sup><\/li><\/ul>\n<ul><li> Being able to extend the study dataset through linking to other data sources has the potential to enable the important research questions for the study to be better answered, with the added benefit of generally reducing the burden on respondents.<sup id=\"rdp-ebb-cite_ref-SoloffEnhancing07_9-0\" class=\"reference\"><a href=\"#cite_note-SoloffEnhancing07-9\" rel=\"external_link\">[9]<\/a><\/sup><\/li><\/ul>\n<p>To enable reuse, data must be well preserved. Community standards for data description and exchange are crucial as these facilitate data reuse by making it easier to import, export, compare, combine and understand data.<sup id=\"rdp-ebb-cite_ref-LynchHow08_3-2\" class=\"reference\"><a href=\"#cite_note-LynchHow08-3\" rel=\"external_link\">[3]<\/a><\/sup> As Pisani (2010)<sup id=\"rdp-ebb-cite_ref-PisaniSharing10_2-4\" class=\"reference\"><a href=\"#cite_note-PisaniSharing10-2\" rel=\"external_link\">[2]<\/a><\/sup> states improved documentation will lead to data being combined more easily across time, locations and sources.\n<\/p><p>The development of <a href=\"https:\/\/www.limswiki.org\/index.php\/Public_health_informatics\" title=\"Public health informatics\" target=\"_blank\" class=\"wiki-link\" data-key=\"f0372a80f101e9f6fd00490dc1ebcedd\">public health information systems<\/a> requires an understanding of the principles, practices, structures and settings in which these systems operate.<sup id=\"rdp-ebb-cite_ref-ReederReusable11_10-0\" class=\"reference\"><a href=\"#cite_note-ReederReusable11-10\" rel=\"external_link\">[10]<\/a><\/sup> Issues of conflicting data standards, the need for interoperable tools for exchanging and sharing data and the need for innovative solutions to address integrated disease surveillance, among many other issues, are driving forces to formalize design strategies in public health information.<sup id=\"rdp-ebb-cite_ref-ReederReusable11_10-1\" class=\"reference\"><a href=\"#cite_note-ReederReusable11-10\" rel=\"external_link\">[10]<\/a><\/sup> Details regarding the specific design and features of such databases are not readily available in the literature and yet, this type of practical information would be valuable for clinicians and researchers who wish to design database systems tailored to their particular requirements.<sup id=\"rdp-ebb-cite_ref-AckermanInt05_4-1\" class=\"reference\"><a href=\"#cite_note-AckermanInt05-4\" rel=\"external_link\">[4]<\/a><\/sup>\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Methods\">Methods<\/span><\/h2>\n<p>The conceptualization of the Public Health Data Management System (PHRDMS) occurred through a series of consultative meetings between public health researchers, information technology business intelligence specialists and data managers. The Public Health Data Management System (PHRDMS) stores data, metadata and documents that are generated throughout the lifecycle of research projects. The PHRDMS provides a structure to allow research data to be maintained in accordance with a large number of laws, regulations and conventions, and was designed specifically to meet the standards of: University of South Australia, (2012) UniSA Framework for the Responsible Conduct of Research<sup id=\"rdp-ebb-cite_ref-USAUniSA12_11-0\" class=\"reference\"><a href=\"#cite_note-USAUniSA12-11\" rel=\"external_link\">[11]<\/a><\/sup>, James Cook University, (2012) Code of Conduct<sup id=\"rdp-ebb-cite_ref-JCUCode12_12-0\" class=\"reference\"><a href=\"#cite_note-JCUCode12-12\" rel=\"external_link\">[12]<\/a><\/sup>, and National Health and Medical Research Council, (2007) Australian Code for the Responsible Conduct of Research. <sup id=\"rdp-ebb-cite_ref-NHMRCAust07_13-0\" class=\"reference\"><a href=\"#cite_note-NHMRCAust07-13\" rel=\"external_link\">[13]<\/a><\/sup> The guidelines were synthesised into the following core set, that have underpinned the development of the PHRDMS:\n<\/p>\n<ul><li> Researchers should retain research data and primary materials for sufficient time to allow reference to them by other researchers and interested parties. For published research data, this may be for as long as interest and discussion persist following publication. <\/li><\/ul>\n<ul><li> When considering how long research data and primary materials are to be retained, the researcher must take account of professional standards, legal requirements and contractual arrangements. <\/li><\/ul>\n<ul><li> Research data should be made available for use by other researchers unless this is prevented by ethical, privacy or confidentiality matters. <\/li><\/ul>\n<ul><li> Research data should be retained for at least the minimum period specified in the institutional policy. <\/li><\/ul>\n<ul><li> The institutional policy on the secure and safe disposal of primary materials and research data must be followed (note that for patient records these are to be kept indefinitely).<\/li><\/ul>\n<ul><li> Researchers must manage research data and primary materials in accordance with the policy of the institution. <\/li><\/ul>\n<ul><li> Sufficient materials and data are retained to justify the outcomes of the research and to defend them if they are challenged. That security and confidentiality of the data is undertaken and maintained. <\/li><\/ul>\n<ul><li> Keep clear and accurate records of the research methods and data sources, including any approvals granted, during and after the research process. <\/li><\/ul>\n<ul><li> Ensure that research data and primary materials are kept in safe and secure storage provided, even when not in current use. <\/li><\/ul>\n<ul><li> Provide the same level of care and protection to primary research records, such as <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_notebook\" title=\"Laboratory notebook\" target=\"_blank\" class=\"wiki-link\" data-key=\"be60c7be96aba8e9a84537fd8835fa54\">laboratory notebooks<\/a>, as to the analysed research data. <\/li><\/ul>\n<ul><li> Retain research data, including electronic data, in a durable, indexed and retrievable form. <\/li><\/ul>\n<ul><li> Maintain a catalogue of research data in an accessible form. <\/li><\/ul>\n<ul><li> Manage research data and primary materials according to ethical protocols and relevant legislation. <\/li><\/ul>\n<ul><li> Maintain confidentiality of research data and primary materials. Researchers given access to confidential information must maintain that confidentiality. <\/li><\/ul>\n<ul><li> Primary materials and confidential research data must be kept in secure storage. Confidential information must only be used in ways agreed with those who provided it. Particular care must be exercised when confidential data are made available for discussion.<\/li><\/ul>\n<p><br \/>\nThe PHRDMS was constructed by the Information Strategy and Technology Services Unit within the University of South Australia through consultation with population health researchers. During the design phase of the PHRDMS, specific researcher requirements were identified, these included:\n<\/p>\n<ul><li> Ensure data is accessible to who need it: including remote regions, different universities.<\/li><\/ul>\n<ul><li> Easily used by researchers as it fits with their business process Eg. Data entry forms look like the questionnaire.<\/li><\/ul>\n<ul><li> Ability to deidentify \/ reidentify participants if necessary.<\/li><\/ul>\n<ul><li> Ability to link data from other sources.<\/li><\/ul>\n<ul><li> Ability to create reports for: individual participants, communities, health services, projects.<\/li><\/ul>\n<ul><li> Allow for version control of project documents and derived datasets.<\/li><\/ul>\n<ul><li> Data fits with International\/ national standards where possible.<\/li><\/ul>\n<ul><li> Temporal view of data.<\/li><\/ul>\n<ul><li> Logging of data extracts.<\/li><\/ul>\n<ul><li> Formal process of data upload and extraction.<\/li><\/ul>\n<ul><li> Metadata development, cleaning, maintenance.<\/li><\/ul>\n<ul><li> Developing and implementing protocols regarding storage, retrieval, security and integrity of the data to be used by key stakeholders. <\/li><\/ul>\n<h2><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h2>\n<p>All of the data, metadata and documents that form part of any public health research project are captured within the PHRDMS. As can be seen in Figure 1 this includes ethics agreements, reports, questionnaires, methods, approvals, publications, data dictionary, and study protocols. \n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_vanGanns_eJHI2015_9-1.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"fe76c52aa2f4822e8aef18ea1abd461f\"><img alt=\"Fig1 vanGanns eJHI2015 9-1.jpg\" src=\"https:\/\/www.limswiki.org\/images\/5\/5a\/Fig1_vanGanns_eJHI2015_9-1.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 1.<\/b> Data, Metadata and Documents that are captured within the Public Health Research Data Management System<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>A copy of the plain language statement for each research project, as required by ethical standards of research, is held within the PHRDM System as a .pdf file. Participant consent agreements are stored as a .pdf file for each project participant within the PHRDM System. Through the security structure of the PHRDM System research participants are deidentified however the system also has the capability to make data reidentifiable (to system administrator roles only) so that reports can be sent to individual participants, participants can be contacted for further involvement in research projects, and also for data linkage purposes. \n<\/p><p>The participant\u2019s consent agreements often have a series of statements relating to particular data \/ information and the participant can choose to consent to the individual statements. These statements often reflect being contacted for further research projects, having the participants data forwarded on to their primary health care clinic etc. These statements are captured with the participants consent within the PHRDM System, so that the agreement between the participant and the project can be maintained during data extraction and reporting. The research projects often have agreements with Communities, Primary Health Care Clinics, hospitals, data custodians etc. Copies of these agreements are held as .pdfs within the PHRDM System for each research project. \n<\/p><p>One of the added features of the PHRDMS is that it also maintains an audit trail and history of all data modifications. The audit trail begins from the time the data has been entered into the system and all modifications to the data are recorded in audit tables which are maintained as part of the system. The audit tables are a log of the change that has been made to the data, at what time and by who. Data that has been manually entered into the database can be corrected through the data entry screens and bulk uploaded data will be backed out of the PHRDM system and then reloaded. \n<\/p><p>All surveys\/ questionnaires that are used within a research project undergo an ethics approval process before they are administered. Sometimes a single survey\/questionnaire will undergo a number of revisions. All versions of the surveys\/questionnaires that have been used within the research project are maintained within the PHRDM System. \n<\/p><p>The PHRDMS stores demographic, vaccinations, diagnosed chronic conditions, medications, lifestyle measures, pathology results, mental health, management plans, allied health and specialist referrals, gestational data and child data. The system allows the system administrator to add clinical variables as needed by the research project, as well as surveys.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Design\">Design<\/span><\/h3>\n<p>The PHRDMS is a very flexible user friendly system. The data model that underlies the PHRDMS is based on three distinct entities and the relationships between them (Figure 2). This data model allows users to customise their view of the database to the variables that they are collecting for their own research project. Users can therefore add new variables to the participant, community, or Primary Health Care Centre entity. The system also allows new questions and answers from questionnaires to be added. The PHRDMS does not store derived variables, only raw data, which allows the users to classify the data according to individual researcher requirements.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_vanGanns_eJHI2015_9-1.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"0480598f61136bdda3f1b8d937f18d92\"><img alt=\"Fig2 vanGanns eJHI2015 9-1.jpg\" src=\"https:\/\/www.limswiki.org\/images\/1\/18\/Fig2_vanGanns_eJHI2015_9-1.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 2.<\/b> The Entities within the Public Health Research Data Management System<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>The PHRDM System produces a number of standard research reports and individual clinical variables can be extracted into an excel spreadsheet. The system also allows codes to be assigned to data so that it can be used directly within Stata<sup id=\"rdp-ebb-cite_ref-NHMRCAust07_13-1\" class=\"reference\"><a href=\"#cite_note-NHMRCAust07-13\" rel=\"external_link\">[13]<\/a><\/sup> once it has been extracted from the system. The system also produces a log report to capture the history of changes made to the data within the system due to data corrections. All data extracts are recorded within the PHRDMS to maintain a history of what data was extracted by who, at what time, for what purpose. \n<\/p><p>The PHRDM system allows for data linkage to external data sets. Data from external data custodians is able to be linked to the participant, community, primary health care centre, or the participant\u2019s pathology result. The data is initially held in a staging area while it is reviewed against the current set of data variable rules. Any external data that does not match the existing data variable rules is able to be reviewed by the system administrator and either be corrected (in the case of a data error) or rejected from the data upload. The data upload and cleansing process is captured within the PHRDMS to maintain an activity log for administration purposes. \n<\/p><p>Due to the nature of Public Health research many of the projects contained within the PHRDMS collect the same clinical variables and often administer the same questionnaires. The PHRDMS maintains projects separately but with many of the research staff working across numerous projects it is possible for data to be viewed as a total collection (Figure 3), allowing for variables from a number of projects to be reused to answer new research questions.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_vanGanns_eJHI2015_9-1.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"e5b7c29426d101944e1af79384b03eb6\"><img alt=\"Fig3 vanGanns eJHI2015 9-1.jpg\" src=\"https:\/\/www.limswiki.org\/images\/f\/f7\/Fig3_vanGanns_eJHI2015_9-1.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 3.<\/b> The Relationship between projects within the Public Health Research Data Management System<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h3><span class=\"mw-headline\" id=\"Access\">Access<\/span><\/h3>\n<p>Initial access to the database is provided through the Australian Access Federation, which will allow researchers into the database, who belong to institutions that are registered with the Australian Access Federation. Therefore allowing researchers access to the system anywhere they are able to get access to the internet. Researchers are then able to be granted access to project data for which they have signed project confidentiality agreements. Access to the project data is then governed by the role that is assigned by the system administrator. The PHRDMS manages data access through the following roles: System Administrator, Researcher, and Data Entry. Functionality within the database is applied to each role with all roles other than system administrator being applied to a specific project.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusion\">Conclusion<\/span><\/h2>\n<p>The Public Health Data Management System stores and manages a large cohort of Indigenous adults and children, both \u201cwell\u201d and who already have a chronic condition on study enrolment. The dataset will grow due to recruitment of participants over time and increase in scope as new datasets are linked to the cohort. The information generated from the system will be used for the immediate research aims of the Centre of Research Excellence in Prevention of Chronic Conditions and will be able to be used by researchers into the future to answer a much broader range of policy relevant questions, including monitoring incidence of renal, cardiovascular disease, diabetes and mental health problems in different risk groups. This cohort will include these participants at baseline, but also be able to identify incidence of disease in those free of problems at recruitment. \n<\/p><p>The design and development of the Public Health Research Data Management System highlights how it is possible to construct an information system which allows greater access to well preserved public health research data to enable it to be reused and shared. While the development of the PHRDMS has been based on Australian guidelines, the conceptual model under pinning the PHRDMS which is based on the three main entities: participant, community and health service could be used internationally.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>The research reported in this paper is a project of the Australian Primary Health Care Research Institute, which is supported by a grant from the Commonwealth of Australia as represented by the Department of Health. The information and opinions contained in it do not necessarily reflect the views or policy of the Australian Primary Health Care Research Institute or the Australian Government Department of Health.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conflicts_of_interest\">Conflicts of interest<\/span><\/h2>\n<p>None declared.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Correspondence\">Correspondence<\/span><\/h2>\n<p><b>Dr Deborah van Gaans (Corresponding Author)<\/b><br \/>\nManager: Research Data<br \/>\nCentre for Research Excellence in the Prevention of Chronic Conditions in Rural and Remote Populations<br \/>\nSchool of Population Health, University of South Australia<br \/>\nLevel 8, South Australian Health & Medical Research Institute (SAMHRI)<br \/>\nNorth Terrace, Adelaide, 5001<br \/>\nTel: +618 830 22908<br \/>\ndeborah.vangaans@unisa.edu.au<br \/>\n<\/p><p>Research Associate<br \/>\nDept. of Geography, Environment and Population,<br \/>\nThe University of Adelaide,<br \/>\nNorth Terrace, Adelaide, South Australia, 5005<br \/>\n<\/p><p><b>Dr Katina D\u2019Onise<\/b><br \/>\nSenior Research Fellow<br \/>\nCentre for Research Excellence in the Prevention of Chronic Conditions in Rural and Remote Populations<br \/>\nSchool of Population Health, University of South Australia<br \/>\nLevel 8, South Australian Health & Medical Research Institute (SAMHRI)<br \/>\nNorth Terrace, Adelaide, 5001<br \/>\nTel: +618 830 21221<br \/>\nkatina.d\u2019onise@unisa.edu.au<br \/>\n<\/p><p><b>Mr. Tony Cardone<\/b><br \/>\nBusiness Intelligence Specialist<br \/>\nChancellery,<br \/>\nBusiness Intelligence and Planning, University of South Australia<br \/>\nCity West Campus<br \/>\nNorth Terrace, Adelaide, 5001<br \/>\nTel: +618 830 27286<br \/>\ntony.cardone@unisa.edu.au<br \/>\n<\/p><p><b>Prof Robyn McDermott<\/b><br \/>\nProfessor of Public Health Medicine<br \/>\nCollege of Public Health, Medical and Veterinary Sciences<br \/>\nJames Cook University, PO Box 6811, Cairns QLD<br \/>\n4870 Australia<br \/>\nTel (07) 4232 1575<br \/>\nrobyn.mcdermott@jcu.edu.au<br \/>\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<ol class=\"references\">\n<li id=\"cite_note-ThompsonTheQual12-1\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-ThompsonTheQual12_1-0\" rel=\"external_link\">1.0<\/a><\/sup> <sup><a href=\"#cite_ref-ThompsonTheQual12_1-1\" rel=\"external_link\">1.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Thompson, S.C.; Woods, J.A.; Katzenellenbogen, J.M. 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[<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.iassistdata.org\/iq\/reduce-reuse-recycle-issues-secondary-use-research-data\" target=\"_blank\">http:\/\/www.iassistdata.org\/iq\/reduce-reuse-recycle-issues-secondary-use-research-data<\/a> \"Reduce, reuse, recycle: Issues\nin the secondary use of research data\"]. <i>IASSIST Quarterly<\/i> <b>29<\/b> (Spring): 5<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.iassistdata.org\/iq\/reduce-reuse-recycle-issues-secondary-use-research-data\" target=\"_blank\">http:\/\/www.iassistdata.org\/iq\/reduce-reuse-recycle-issues-secondary-use-research-data<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Reduce%2C+reuse%2C+recycle%3A+Issues%0Ain+the+secondary+use+of+research+data&rft.jtitle=IASSIST+Quarterly&rft.aulast=Law%2C+Margaret&rft.au=Law%2C+Margaret&rft.volume=29&rft.issue=Spring&rft.pages=5&rft_id=http%3A%2F%2Fwww.iassistdata.org%2Fiq%2Freduce-reuse-recycle-issues-secondary-use-research-data&rfr_id=info:sid\/en.wikipedia.org:Journal:The_development_of_the_Public_Health_Research_Data_Management_System\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-ElgerStrat10-7\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-ElgerStrat10_7-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Elger, B.S.; Iavindrasana, J.; Iacono, L.L. et al.. \"Strategies for health data exchange for secondary, cross-institutional clinical research\". <i>Computer Methods and Programs in Biomedicine<\/i> <b>99<\/b> (3): 230\u2013251. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.cmpb.2009.12.001\" target=\"_blank\">10.1016\/j.cmpb.2009.12.001<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20089327\" target=\"_blank\">20089327<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Strategies+for+health+data+exchange+for+secondary%2C+cross-institutional+clinical+research&rft.jtitle=Computer+Methods+and+Programs+in+Biomedicine&rft.aulast=Elger%2C+B.S.%3B+Iavindrasana%2C+J.%3B+Iacono%2C+L.L.+et+al.&rft.au=Elger%2C+B.S.%3B+Iavindrasana%2C+J.%3B+Iacono%2C+L.L.+et+al.&rft.volume=99&rft.issue=3&rft.pages=230%E2%80%93251&rft_id=info:doi\/10.1016%2Fj.cmpb.2009.12.001&rft_id=info:pmid\/20089327&rfr_id=info:sid\/en.wikipedia.org:Journal:The_development_of_the_Public_Health_Research_Data_Management_System\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-PiwowarTowards08-8\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-PiwowarTowards08_8-0\" rel=\"external_link\">8.0<\/a><\/sup> <sup><a href=\"#cite_ref-PiwowarTowards08_8-1\" rel=\"external_link\">8.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Piwowar, H.A.; Becich, M.J.; Bilofsky, H.; Crowley, R.S.; caBIG Data Sharing and Intellectual Capital Workspace. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2528049\" target=\"_blank\">\"Towards a data sharing culture: Recommendations for leadership from academic health centers\"<\/a>. <i>PLoS Medicine<\/i> <b>5<\/b> (9): e183. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1371%2Fjournal.pmed.0050183\" target=\"_blank\">10.1371\/journal.pmed.0050183<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2528049\/\" target=\"_blank\">PMC2528049<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18767901\" target=\"_blank\">18767901<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2528049\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2528049<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Towards+a+data+sharing+culture%3A+Recommendations+for+leadership+from+academic+health+centers&rft.jtitle=PLoS+Medicine&rft.aulast=Piwowar%2C+H.A.%3B+Becich%2C+M.J.%3B+Bilofsky%2C+H.%3B+Crowley%2C+R.S.%3B+caBIG+Data+Sharing+and+Intellectual+Capital+Workspace&rft.au=Piwowar%2C+H.A.%3B+Becich%2C+M.J.%3B+Bilofsky%2C+H.%3B+Crowley%2C+R.S.%3B+caBIG+Data+Sharing+and+Intellectual+Capital+Workspace&rft.volume=5&rft.issue=9&rft.pages=e183&rft_id=info:doi\/10.1371%2Fjournal.pmed.0050183&rft_id=info:pmc\/PMC2528049&rft_id=info:pmid\/18767901&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2528049&rfr_id=info:sid\/en.wikipedia.org:Journal:The_development_of_the_Public_Health_Research_Data_Management_System\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SoloffEnhancing07-9\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SoloffEnhancing07_9-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Soloff, C.; Sanson, A.; Wake, M.; Harrison, L.. \"Enhancing longitudinal studies by linkage to national databases: <i>Growing Up in Australia<\/i>, the longitudinal study of Australian children\". <i>International Journal of Social Research Methodology<\/i> <b>10<\/b> (5): 349\u2013363. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F13645570701677060\" target=\"_blank\">10.1080\/13645570701677060<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Enhancing+longitudinal+studies+by+linkage+to+national+databases%3A+%27%27Growing+Up+in+Australia%27%27%2C+the+longitudinal+study+of+Australian+children&rft.jtitle=International+Journal+of+Social+Research+Methodology&rft.aulast=Soloff%2C+C.%3B+Sanson%2C+A.%3B+Wake%2C+M.%3B+Harrison%2C+L.&rft.au=Soloff%2C+C.%3B+Sanson%2C+A.%3B+Wake%2C+M.%3B+Harrison%2C+L.&rft.volume=10&rft.issue=5&rft.pages=349%E2%80%93363&rft_id=info:doi\/10.1080%2F13645570701677060&rfr_id=info:sid\/en.wikipedia.org:Journal:The_development_of_the_Public_Health_Research_Data_Management_System\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-ReederReusable11-10\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-ReederReusable11_10-0\" rel=\"external_link\">10.0<\/a><\/sup> <sup><a href=\"#cite_ref-ReederReusable11_10-1\" rel=\"external_link\">10.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Reeder, B.; Hills, R.A.; Demiris, G.; Revere, D.; Pina, J.. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3053242\" target=\"_blank\">\"Reusable design: A proposed approach to public health informatics system design\"<\/a>. <i>BMC Public Health<\/i> <b>11<\/b>: 116. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2458-11-116\" target=\"_blank\">10.1186\/1471-2458-11-116<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3053242\/\" target=\"_blank\">PMC3053242<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21333000\" target=\"_blank\">21333000<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3053242\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3053242<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Reusable+design%3A+A+proposed+approach+to+public+health+informatics+system+design&rft.jtitle=BMC+Public+Health&rft.aulast=Reeder%2C+B.%3B+Hills%2C+R.A.%3B+Demiris%2C+G.%3B+Revere%2C+D.%3B+Pina%2C+J.&rft.au=Reeder%2C+B.%3B+Hills%2C+R.A.%3B+Demiris%2C+G.%3B+Revere%2C+D.%3B+Pina%2C+J.&rft.volume=11&rft.pages=116&rft_id=info:doi\/10.1186%2F1471-2458-11-116&rft_id=info:pmc\/PMC3053242&rft_id=info:pmid\/21333000&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC3053242&rfr_id=info:sid\/en.wikipedia.org:Journal:The_development_of_the_Public_Health_Research_Data_Management_System\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-USAUniSA12-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-USAUniSA12_11-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/w3.unisa.edu.au\/RES\/ethics\/integrity\/default.asp\" target=\"_blank\">\"UniSA Framework for the Responsible Conduct of Research\"<\/a>. University of South Australia. 2012<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/w3.unisa.edu.au\/RES\/ethics\/integrity\/default.asp\" target=\"_blank\">http:\/\/w3.unisa.edu.au\/RES\/ethics\/integrity\/default.asp<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 26 November 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=UniSA+Framework+for+the+Responsible+Conduct+of+Research&rft.atitle=&rft.date=2012&rft.pub=University+of+South+Australia&rft_id=http%3A%2F%2Fw3.unisa.edu.au%2FRES%2Fethics%2Fintegrity%2Fdefault.asp&rfr_id=info:sid\/en.wikipedia.org:Journal:The_development_of_the_Public_Health_Research_Data_Management_System\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-JCUCode12-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-JCUCode12_12-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.jcu.edu.au\/policy\/governance\/conduct\/JCUDEV_007161.html\" target=\"_blank\">\"Code of Conduct\"<\/a>. James Cook University. 2012<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.jcu.edu.au\/policy\/governance\/conduct\/JCUDEV_007161.html\" target=\"_blank\">http:\/\/www.jcu.edu.au\/policy\/governance\/conduct\/JCUDEV_007161.html<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 26 November 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Code+of+Conduct&rft.atitle=&rft.date=2012&rft.pub=James+Cook+University&rft_id=http%3A%2F%2Fwww.jcu.edu.au%2Fpolicy%2Fgovernance%2Fconduct%2FJCUDEV_007161.html&rfr_id=info:sid\/en.wikipedia.org:Journal:The_development_of_the_Public_Health_Research_Data_Management_System\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-NHMRCAust07-13\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-NHMRCAust07_13-0\" rel=\"external_link\">13.0<\/a><\/sup> <sup><a href=\"#cite_ref-NHMRCAust07_13-1\" rel=\"external_link\">13.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\"> (PDF) <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.nhmrc.gov.au\/_files_nhmrc\/publications\/attachments\/r39_australian_code_responsible_conduct_research_150107.pdf\" target=\"_blank\"><i>Australian Code for the Responsible Conduct of Research<\/i><\/a>. National Health and Medical Research Council, Australian Government. 2007. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" target=\"_blank\">ISBN<\/a> 1864964383<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.nhmrc.gov.au\/_files_nhmrc\/publications\/attachments\/r39_australian_code_responsible_conduct_research_150107.pdf\" target=\"_blank\">https:\/\/www.nhmrc.gov.au\/_files_nhmrc\/publications\/attachments\/r39_australian_code_responsible_conduct_research_150107.pdf<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 26 November 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Australian+Code+for+the+Responsible+Conduct+of+Research&rft.date=2007&rft.pub=National+Health+and+Medical+Research+Council%2C+Australian+Government&rft.isbn=1864964383&rft_id=https%3A%2F%2Fwww.nhmrc.gov.au%2F_files_nhmrc%2Fpublications%2Fattachments%2Fr39_australian_code_responsible_conduct_research_150107.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:The_development_of_the_Public_Health_Research_Data_Management_System\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. The figures have been moved around slightly to be closer to their reference in the text.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192209\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.382 seconds\nReal time usage: 0.413 seconds\nPreprocessor visited node count: 11735\/1000000\nPreprocessor generated node count: 34182\/1000000\nPost\u2010expand include size: 94770\/2097152 bytes\nTemplate argument size: 31337\/2097152 bytes\nHighest expansion depth: 18\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 383.989 1 - -total\n 75.91% 291.487 1 - Template:Reflist\n 63.33% 243.177 13 - Template:Citation\/core\n 55.60% 213.487 10 - Template:Cite_journal\n 16.90% 64.881 1 - Template:Infobox_journal_article\n 16.19% 62.167 1 - Template:Infobox\n 9.50% 36.469 80 - Template:Infobox\/row\n 8.17% 31.382 22 - Template:Citation\/identifier\n 8.02% 30.807 2 - Template:Cite_web\n 5.41% 20.755 1 - Template:Cite_book\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:7949-0!*!0!!en!5!* and timestamp 20181214192208 and revision id 23910\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:The_development_of_the_Public_Health_Research_Data_Management_System\">https:\/\/www.limswiki.org\/index.php\/Journal:The_development_of_the_Public_Health_Research_Data_Management_System<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","8b00807d95773df324df7278fa97c909_images":["https:\/\/www.limswiki.org\/images\/5\/5a\/Fig1_vanGanns_eJHI2015_9-1.jpg","https:\/\/www.limswiki.org\/images\/1\/18\/Fig2_vanGanns_eJHI2015_9-1.jpg","https:\/\/www.limswiki.org\/images\/f\/f7\/Fig3_vanGanns_eJHI2015_9-1.jpg"],"8b00807d95773df324df7278fa97c909_timestamp":1544815328,"5405bb942ce8b77cfcb5385454aa4c95_type":"article","5405bb942ce8b77cfcb5385454aa4c95_title":"No specimen left behind: Industrial scale digitization of natural history collections (Blagoderov et al. 2012)","5405bb942ce8b77cfcb5385454aa4c95_url":"https:\/\/www.limswiki.org\/index.php\/Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections","5405bb942ce8b77cfcb5385454aa4c95_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:No specimen left behind: Industrial scale digitization of natural history collections\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nNo specimen left behind: Industrial scale digitization of natural history collectionsJournal\n \nZooKeysAuthor(s)\n \nBlagoderov, V.; Kitching, I.J.; Livermore, L.; Simonsen, T.J.; Smith, V.S.Author affiliation(s)\n \nNatural History Museum - LondonPrimary contact\n \nE-mail: v.blagoderov@nhm.ac.ukEditors\n \nPenev, L.Year published\n \n2012Volume and issue\n \n209Page(s)\n \n133-146DOI\n \n10.3897\/zookeys.209.3178ISSN\n \n1313-2970Distribution license\n \nCreative Commons Attribution 3.0 UnportedWebsite\n \nhttp:\/\/zookeys.pensoft.net\/articles.php?id=2916Download\n \nClick \"PDF\" button on website to generate\n\nContents\n\n1 Abstract \n2 Introduction \n3 Methods \n\n3.1 Imaging \n3.2 Metadata capture \n3.3 Assigning uIDs \n\n\n4 Results \n5 Discussion \n6 Acknowledgements \n7 References \n8 Appendix 1 \n9 Notes \n\n\n\nAbstract \nTraditional approaches for digitizing natural history collections, which include both imaging and metadata capture, are both labour- and time-intensive. Mass-digitization can only be completed if the resource-intensive steps, such as specimen selection and databasing of associated information, are minimized. Digitization of larger collections should employ an \u201cindustrial\u201d approach, using the principles of automation and crowd sourcing, with minimal initial metadata collection including a mandatory persistent identifier. A new workflow for the mass-digitization of natural history museum collections based on these principles, and using SatScan\u00ae tray scanning system, is described.\nKeywords: Digitization, imaging, specimen metadata, natural history collections, biodiversity informatics\n\nIntroduction \nNatural history collections are of immense scientific and cultural importance. Specimens in public museums and herbaria and their associated data represent a potentially vast repository of information on biodiversity, ecosystems and natural resources for the widest range of stakeholders, from governments and NGOs to schools and private individuals. Numerous examples of the uses to which biodiversity data derived from natural history collections have been put in research on evolution and genetics, nature conservation and resource management, public health and safety, and education are widely available (summarized in Chapman 2005, Baird 2010).[1][2] The universe of natural history collection data has been estimated to be between 1.2 and 2.1 \u00d7 109 units (specimens, lots and collections) (Ari\u00f1o 2010).[3] To ensure efficient access, dissemination and exploitation of such an immense wealth of biodiversity relevant data, it is evident that a well-coordinated and streamlined approach to global digitization is required, in particular because it is absolutely essential for the scientific value of the generated data that the outputs (images, metadata, etc.) are linked together and also back to the original specimens via unique identifiers (uIDs).\nIn recent years, substantial efforts and resources have been invested into the digitization of natural history collections, with museums and herbaria routinely employing specimen level collection databases to replace older, paper-based card indexes and ledgers. In theory, this should make dissemination of specimen data through biodiversity informatics portals such as the Global Biodiversity Information Facility (GBIF; http:\/\/www.gbif.org\/) very simple and straightforward. However, the truth is that natural history collections are almost as far from complete digitization as they were 20 years ago. Ari\u00f1o (2010)[3] estimated that no more than 3% of biological specimen data is web-accessible through GBIF, the largest source of biodiversity information. Consequently, there is neither a central database of collection holdings, nor a complete collection index available to users. The reason for this deficiency is partly the immense effort it would take to digitize the vast number of collections units involved (Vollmar et al. 2010).[4] The cost of traditional digitization workflows is vast, both in financial and human terms. Our simple calculations have shown that complete databasing of the ~30 million insect specimens housed in the entomological collection of the Natural History Museum, London, would require 23 years of continuous work from the entire departmental staff to complete (65 people). Depending on the particular collections and curatorial practices used, estimates vary from US$0.50 to several dollars per specimen to capture full label data (Heidorn 2011).[5] The cost of traditional imaging and databasing of every natural history object in all European museums was recently estimated as \u20ac73.44 per object (Poole 2010).[6] Thus, the complete digitization of all natural history collections may cost as much as \u20ac150, 000 million, and take as long as 1,500 years.\nThe most common solution proposed to overcome the enormous cost of digitization is prioritization based on user demand (Berents et al. 2010).[7] Currently, most digitization projects concentrate their efforts on obtaining high quality images of selected specimens accompanied by high quality data (e.g., comprehensive and expertly interpreted label information) rather than total collections coverage. Such specimen-centric digitization efforts are thus inevitably fragmented into numerous small-scale and labour-intensive projects that usually image single specimens, one at a time.\nTo solve the problem of cost, as well as the inherent fragmentation in collection based biodiversity informatics, new, industrial-scale approaches to digitization are clearly needed. The larger a digitization project becomes, the lower are the transaction costs and thus the lower is the cost per specimen. Such an industrial-scale process must necessarily fulfill certain standardized criteria if it is to be of use to and adopted by a wide spectrum of natural history collections:\n\n As much as possible of the procedure must be automated, except when physical handling of specimens is necessary.\n The approach should, whenever possible, focus on \u201cwall-to-wall\u201d total digitization of entire collections, because it is faster to digitize an entire collection than to select individual specimens or drawers of particular interest.\n Complicated labour-intensive procedures must be divided into a series of separate, shorter steps, each with a distinct outcome. For example, preparation of specimens for imaging should be a separate step from the imaging itself; and unique specimen identifiers can be assigned simultaneously to all specimens in a drawer rather than individually and sequentially. Such a modularised process can then be more easily crowd-sourced among the professional and volunteer communities. Properly organized crowd-sourcing projects would be able to mobilise the efforts of thousands of enthusiasts around the world (Hill et al. 2012).[8]\n Collection of metadata must be simplified and standardized. In most cases, digital representation of the specimen and minimal metadata (uID, specimen location in the collection) is sufficient for collection management purposes. Only minimal information should be collected when initially digitizing an entire collection, but in such a way that it can be amended and expanded upon later.\nHere we describe a new method for \u201cwall-to-wall\u201d mass-digitization of natural history museum collections based on the SatScan\u00ae tray scanning system. The method allows for standardized scanning of museum collection trays of the highest image quality possible, followed by simplified (and easily expandable) collection of metadata.\n\nMethods \nThe Natural History Museum (NHM), London, has been working with SmartDrive Limited (http:\/\/www.smartdrive.co.uk\/) since 2009 on the development of one of the company\u2019s products, the SatScan\u00ae collection scanner (Fig. 1). From this collaboration, we have developed a workflow that we consider meets our needs for the industrial-scale digitization of a significant part of the NHM\u2019s collections. The system is particularly suited to the digitization of multiple, uniformly mounted or laid out specimens, such as pinned insects and smaller geological or mineralogical objects in standardized collection drawers, horizontally-stored microscope slides and herbarium sheets.\n\n\n\n\n\n\n\n\n\n Figure 1. SatScan imaging: a SatScan machine b specimens being imaged c individual frames aligned d fragment of a stitched image; final resolution of the stitched image ~11 lines\/mm\n\n\n\nThe digitization workflow envisioned for the NHM (Fig. 2) comprises three steps:\n\n\n\n\n\n\n\n\n\n Figure 2. Image based digitization workflow consisting of four stages: Imaging, Metadata capture, Institutional databasing and Publication\n\n\n\nImaging \nThe SatScan\u00ae collection scanner is capable of producing high-resolution images of entire collection drawers (see Table 1, Blagoderov et al. 2010, Mantle et al. 2012).[9][10] The specific configuration of the system has changed somewhat from that described in the report, such that now a USB CMOS UEye-SE camera (model # UI-1480SE-C-HQ, 2560\u00d71920 resolution) is used in combination with Edmund Optics telecentric TML lenses of 0.3\u00d7 (#58428) and 0.16\u00d7 TML (#56675). A camera with attached lens is moved in two dimensions along precision-engineered rails positioned above the object to be imaged. A combination of hardware and software provides automated capture of high resolution images of small regions of interest, which are then assembled (\u201cstitched\u201d) into a larger panoramic image, generating the final image of the entire drawer. This method maximizes depth of field of the captured images and minimizes distortion and parallax artefacts. Analogous solutions for large-area imaging which have been developed independently include GigaPan (Bertone et al. 2012)[11], MicroGigaPan (Longson et al. 2010)[12] and DScan (Schmidt et al. 2012).[13]\n\n\n\n\n\n\n\nTable 1. Resolution and depth of field of the system as compared with a Canon EOS450D DSLR camera using a Canon MP E-65 macrolens (USAF: the smallest resolvable element on 1951 US Air Force resolution test chart; MRD: minimal resolved distance, size of the smallest visible object on image)\n\n\nObjective\n\nSensor Resolution\n\nAperture\n\nDepth of Field, mm\n\nResolution\n\n\nUSAF\n\nLines, mm\n\nMRD, \u03bcm\n\n\nSatScan 0.16\u00d7 lens\n\n1280\u00d7960\n\nOpen\n\n5\n\n3\u20134\n\n11.3\n\n44\n\n\nDot\n\n10\n\n3\u20134\n\n11.3\n\n44\n\n\nClosed\n\n>70\n\n2\u20135\n\n6.35\n\n79\n\n\n2560\u00d71920\n\nOpen\n\n5\n\n4\u20133\n\n20.16\n\n25\n\n\nDot\n\n14\n\n4\u20131\n\n16.0\n\n31\n\n\nClosed\n\n>70\n\n3\u20132\n\n8.89\n\n56\n\n\nSatScan 0.3\u00d7 lens\n\n1280\u00d7960\n\nOpen\n\n2.5\n\n4\u20132\n\n17.95\n\n28\n\n\nDot\n\n4.5\n\n4\u20132\n\n17.95\n\n28\n\n\nClosed\n\n30\n\n3\u20134\n\n11.3\n\n44\n\n\n2560\u00d71920\n\nOpen\n\n1.5\n\n5\u20133\n\n40.3\n\n12\n\n\nDot\n\n3\n\n5\u20132\n\n36.0\n\n14\n\n\nClosed\n\n35\n\n3\u20135\n\n12.7\n\n39\n\n\nCanon MP-E65 lens, 1\u00d7\n\n4272\u00d72848\n\n2.8\n\n0.5\n\n5\u20136\n\n57\n\n8.8\n\n\n16\n\n4\n\n-\n\n-\n\n-\n\n\nCanon MP-E65 lens, 5\u00d7\n\n4272\u00d72848\n\n2.8\n\n<0.3\n\n8\u20131\n\n256\n\n2\n\n\n16\n\n2\n\n6\u20132\n\n71.8\n\n7\n\n\n\nMetadata capture \nA prototype software program, Metadata Creator, has been designed to allow fast capture of specimen data and associating these with the image of the specimen (Fig. 3). Users can mark individual specimens on the panoramic image by drawing rectangular boxes around them, selecting these areas and annotating them individually or in batches. Methods for marking the specimen, editing regions of interest and selection of multiple specimens are analogous to those used in many common graphic applications and so will be familiar, even to inexperienced users.\nSpecimen metadata is captured in a series of fields that are compatible with the Darwin Core 1.4.1 schema (http:\/\/rs.tdwg.org\/dwc\/) and which can be customized to particular user requirements. To maximize throughput, only basic metadata are collected at this stage. These will generally include a unique collection number of every specimen (see below, barcodes), collection identification (to the available curatorial level, e.g. to species\/subspecies for the \u201cMain Collection\u201d and family\/order for unsorted accessions), and, if possible, biogeographic region\/country. Taxon names are looked up from an index derived from the NHM Collections Management Database. A completed project comprises a folder with an archival image of the drawer, full-resolution images of individual specimens cut-out from the drawer image, and an XML file containing annotations and links to specimen images (Appendix 1). Trials have demonstrated that 10\u201320 seconds per specimen is required to capture basic metadata using the Metadata Creator Software. A unique ID for the drawer is also recorded. As the NHM Collection Management System already includes a complete collections index (a brief description of the content of every drawer), no additional information is required.\n\n\n\n\n\n\n\n\n\n Figure 3. Metadata Creator software: a\u2013c working areas a drawer image b specimen records c annotation fields d tool selector e unique IDs\n\n\n\nAssigning uIDs \nEvery specimen is assigned a unique number under which it will be registered in the NHM Collections Management Database. It is a requirement of collections management procedures that a label bearing the specimen\u2019s uID is attached to the specimen. To streamline this part of the process, it is subdivided into the following steps:\n\n A sequence of unique numbers is generated from the NHM Collections Management Database.\n Labels that include both a human-readable number and a machine-readable barcode are printed.\n The operator labels the specimens by selecting a specimen on the drawer image, pinning a label under the specimen, and scanning the barcode, thereby adding the uID into the corresponding field of Metadata Creator. Barcodes can be pinned facing up or down depending on curatorial practice; the former has the advantage of visibility on the image. In this case imaging, of course, has to take place after assigning uIDs. Images of individual specimens for which the metadata have been collected and individual numbers assigned are automatically marked on the drawer image with a grey spot, allowing easy visualization of progress.\n When all specimens have been labelled and recorded, the XML file and corresponding specimen images are imported into the NHM Collections Management Database.\nWe must emphasize that Metadata Creator is a prototype software application; much more development is needed for to perfect its functionality, user interface, and integration with the Museum\u2019s information systems.\n\nResults \nA preliminary assessment of the SatScan\u00ae system was undertaken and reported upon by Blagoderov et al. (2010).[9] Based on their findings, a series of recommendations were made for improvements and possible longer term developments to the hardware, software, imaging system and ergonomics. An updated system was delivered to the NHM in September 2011 and further trials were then conducted. This newer version of SatScan\u00ae provides non-extrapolated resolution of the final images from 11.3 to 40.3 lines\/mm and a minimum resolved distance of 79 to 12\u03bcm, depending on the lens and sensor settings employed (Table 1). The maximum depth of field has been increased slightly from 80mm to 85mm. Although focus stacking is implemented in the current version of the system, in most cases it is not necessary. For the majority of collections drawers, specimens are presented at a more-or-less uniform height and within the available depth of field; focus stacking is really only necessary for those drawers where specimens are pinned at markedly different heights or are particularly deep (e.g. fossils and mineralogical samples). The average time to scan a typical collection drawer without focus stacking is between four and six minutes, depending upon size (eight to ten minutes including logistics, Table 2). This generally translates to about two seconds per specimen. Thus, in a working day, an operator could image up to 70 drawers. These would then be stitched into the final images using an overnight batch process (see average figures in Table 2). The resulting images vary in size from 0.3 Gpx to 5 Gpx (109 pixels; 250 MB \u2013 3 GB compressed TIFF files) depending on the imaging area, lens and resolution used. However, use of the highest resolution in mass digitization projects may not always be practical. We did not conduct extensive tests with the highest resolution of camera\/higher magnification of lens because a 64-bit version of software is needed to handle the stitching process for files of this size, and this was not available at the time of trials.\nThe part of the process that involves marking of specimens and metadata capture using Metadata Creator has not been as thoroughly tested and we have yet to trial the part of the procedure that produces barcode labels and attaches these to specimens. However, preliminary results involving mock elements indicate that it will take about ten seconds per specimen. This time will be extended for those specimens that already have a human-readable uID (a \u201cBMNH(E)\u201d number, for example) but no barcode label, because then the former will have to be manually entered into Metadata Creator and a new barcode label printed. However, relatively few NHM insect specimens (about 1.2%) have so far been databased and assigned a uID.\nThe entomology collections of the NHM have about 30 million insect specimens, mostly pinned, housed in 135, 000 collections drawers. Assuming that 80% of the collection is appropriate to be imaged using the SatScan\u00ae system, rough calculations based on the above figures suggest that the entire collection could be imaged and basic metadata captured in 18 person-years.\n\n\n\n\n\n\n\nTable 2. Scanning and stitching times for different types of drawers\n\n\nDrawer type\n\nNumber of drawers in trials\n\nDimensions, mm\n\nNumber of frames\n\nAverage scanning time (including logistics), min\n\nAverage stitching time, min\n\nFile size, Mb\n\n\nMain collection and accessions\n\n236\n\n500\u00d7400 or 470\u00d7450\n\n17\u00d714 or 16\u00d715\n\n8.52\n\n12.65\u00b11.54\n\n488.20\u00b130.21\n\n\nRothschild and Rhopalocera\n\n144\n\n560x540 or 570x 555\n\n21\u00d717 or 22\u00d717\n\n10.13\n\n25.41\u00b14.21\n\n715.90\u00b189.58\n\n\n\nDiscussion \nAlthough images acquired through an industrial digitization process might be considered to be of limited use for taxonomic purposes, because they feature only one aspect of the specimens and may not contain necessary morphological details or label data, they could prove very useful for a variety of other purposes. Obvious collection management applications include improved collection audit and security, as well as improving accessibility of the collection. For research purposes, such acquired images could prove very valuable in morphometric analyses and phenological population studies. In addition, the public engagement aspect of industrial digitization activities should not be underestimated. Online public access to high resolution images and metadata will likely enhance public awareness of the importance of local and national collections (as well as engendering a sense of shared ownership). Moreover, high quality images will open up the possibility for fast and reliable automated or semi-automated specimen identification and thus encourage environmental \u201ccitizen-science\u201d, such as recording distributional or abundance changes of key species.\nMajor problems remaining with the described approach are largely concerned with the time taken to scan specimens\/samples and to collect metadata. Even with a simple approach, scanning a specimen takes approximately two to four seconds followed by 10\u201320s for annotation and\/or barcoding. Furthermore, only basic metadata are collected under the scenario described above. Indeed, in the worst case, say a drawer of unidentified mixed organisms from several phyla, only a uID will be associated with each of the specimens. It may then be argued that this will compel museums and herbaria to create essentially incomplete records with which to populate their collection databases. However, such records are comparable to stub pages in Wikipedia, empty at the moment but capable of being filled and edited in due course. Indeed, there is a case to be made for the opposite viewpoint, that there is no point collecting complete metadata if these are not going to be used for any purpose. Finally, it should be noted that the industrial digitization process described above only works relatively seamlessly for more-or-less uniformly preserved and presented specimens, such pinned insects in drawers and herbarium sheets. It is unlikely to be satisfactory for pickled specimens in jars of ethanol. These collections may have to be digitized using a different protocol.\nApproximately 90% of the time required for digitization is spent on capturing metadata and labelling specimens. While the latter involves physical handling of the specimens and must be performed by experienced staff, selection of specimens in the drawer images and annotation thereof can be undertaken in a virtual environment. In many cases, the basic information to be collected can be seen in the drawer image. Implementing an open source web application that duplicates the functions of Metadata Creator and publication of drawer images using algorithms involving a pyramid of tiles (produced using Zoomify\u2122 (http:\/\/www.zoomify.com\/) or Google Maps (http:\/\/maps.google.com\/), for example) will allow volunteers from around the world to participate in digitization of the collection and will decrease the time needed to process a specimen by at least 50%.\nThe next step in facilitating the digitization process might be to undertake \u201cvirtual curation\u201d. Here, uIDs are assigned to each specimen, records are created in the collection management database and corresponding specimen images linked to these records, but the specimens themselves are not labelled until it becomes necessary to handle the specimen physically for some other purpose (curation, loan, identification, dissection, etc.). Of course, these procedural changes would require a major cultural shift for Collections Management staff.\nRevised, though still simplistic, calculations now show that the entire NHM collection of insects could be imaged in 12.88 person-years and completely digitized without crowd-sourcing in 118 person-years. Collecting basic information and attaching a barcode to a specimen would take approximately 10-30 seconds. Per-specimen cost under the current (2012) economic climate would thus be as low as \u00a30.12. If we limit SatScan-based digitization to large and medium-size insects (up to 5 mm in length), the total time required is 58 man-years. This effort does not seem insuperable considering that the NHM insect collection is managed by 26 permanent curatorial staff, assisted by a number of people in short-term contracts and volunteers.\nDespite the potential perceived drawbacks, image-based basic digitization can nevertheless mobilize hundreds of millions of biological specimens in a relatively short period of time. It is estimated that entomological specimens constitute up to 40% of all natural history specimens (Ari\u00f1o 2010).[3] Some palaeontological, zoological and mineralogical specimens, including microscopic slides, are also stored in collection drawers and trays that are amenable to simultaneous imaging. Thus, the majority of natural history specimens could potentially be digitized using industrial imaging.\nThe return on investment in total collection digitization will be enormous. It will open up collections to the world, facilitating their use, and help create a global collection index that can be used to set priorities for further digitization. Basic digitization of all the world\u2019s holdings of insects (800 million specimens) could be completed in less than 4000 person-years. This may sound like a huge figure, but divided among approximately 1, 300 collections and potentially tens of thousands of professionals and volunteers, the work could be completed much quicker, perhaps in only a few years. \"Furthermore, emerging technologies in the near future will undoubtedly decrease time and costs, while increasing data quality. Complete image-based basic digitization of insect and plant collections would produce at least 30 Pb (1015 bytes) of data, which constitutes ~0.0006% of the current data hosted on the Internet. At \u00a30.2 per specimen, the cost of digitizing 2, 000 million natural history specimens may appear to be an eye-wateringly high figure of \u00a3400 million. However, divided among ~4, 000 natural history collections, this reduces to an average project cost of \u00a3100, 000, which is equivalent to the size of a relatively modest research grant. To this the cost of imaging equipment must be added. At present, a SatScan system costs between \u00a325, 000 and \u00a360, 000, depending on the options to be implemented and the service agreement chosen, but less expensive alternative solutions are also being developed (Bertone et al. 2012, Dietrich et al. 2012, Schmidt et al. 2012).[11][14][13]\nRegardless of the technology used, mass digitization will nevertheless follow the same general approach, which includes mechanisms that enrich digital media with specimen-level metadata. This enrichment will:\n\n Facilitate open dissemination of data so that it can be discovered and accessed by stakeholders, reducing both the need for physical access to collections and the number of loans;\n Enable large-scale manipulation and integration of collection data, supporting stakeholders in their monitoring and management of information on ecosystems, biodiversity and natural resources;\n Enhance curatorial activities, allowing the condition of loans to be tracked and reduce identification inaccuracies;\n Protect biodiversity heritage by reducing the need to handle irreplaceable specimens;\n Improve collections security by providing base-line images against which damage and thefts can be monitored;\n Support disaster management, such that should the worst happen to a collection, its digital representation will continue to provide a valuable resource;\n Raise natural history collections profiles, resulting in improved resources for further research;\n Contribute beyond the traditional remit of museums and herbaria into new areas of interest, particularly education and public understanding of science; and\n Support biodiversity legislation and data repatriation, which is an increasing requirement under both the 1992 Convention on Biological Diversity and the subsequent 2010 Nagoya Protocol on Access and Benefit-sharing.\nAcknowledgements \nThe authors are very grateful to Dennis Murphy, Dave Freer, and Mike Broderick (SmartDrive Ltd.) for fruitful and ongoing collaboration; Chris Raper for help with testing the system and development of software; and two reviewers, in particular Matt Yoder, whose comments and suggestions greatly improved original version of the manuscript.\n\nReferences \n\n\n\u2191 Chapman, A. (2005). \"Uses of Primary Species-Occurrence Data, version 1.0\". Report for the Global Biodiversity Information Facility, Copenhagen. Global Biodiversity Information Facility. pp. 100. http:\/\/www.gbif.org\/resource\/80545 .   \n\n\u2191 Baird, R. (2010). \"Leveraging the fullest potential of scientific collections through digitization\". Biodiversity Informatics 7 (2): 130\u2013136. doi:10.17161\/bi.v7i2.3987.   \n\n\u2191 3.0 3.1 3.2 Ari\u00f1o, A.H. (2010). \"Approaches to estimating the universe of natural History collections data\". Biodiversity Informatics 7 (2): 81\u201392. doi:10.17161\/bi.v7i2.3991.   \n\n\u2191 Vollmar, A.; Macklin, J.A.; Ford, L. (2010). \"Natural history specimen digitization: Challenges and concerns\". Biodiversity Informatics 7 (2): 93\u2013112. doi:10.17161\/bi.v7i2.3992.   \n\n\u2191 Heidorn, P.B. (2011). \"Biodiversity informatics\". Bulletin of the American Society for Information Science and Technology 37 (6): 38\u201344. doi:10.1002\/bult.2011.1720370612.   \n\n\u2191 Poole, N. (November 2010). \"The Cost of Digitising Europe's Cultural Heritage\". Collections Trust. pp. 82. http:\/\/www.collectionstrust.org.uk\/item\/739-the-cost-of-digitising-europe-s-cultural-heritage .   \n\n\u2191 Berents, P.; Hamer, M.; Chavan, V. (2010). \"Towards demand driven publishing: Approches to the prioritisation of digitisation of natural history collections data\". Biodiversity Informatics 7 (2): 113\u2013119. doi:10.17161\/bi.v7i2.3990.   \n\n\u2191 Hill, A.; Guralnick, R.; Smith, A. (2012). \"The notes from nature tool for unlocking biodiversity records from museum records through citizen science\". ZooKeys 209: 219\u2013233. doi:10.3897\/zookeys.209.3472.   \n\n\u2191 9.0 9.1 Blagoderov, V.; Kitching, I.; Simonsen, T.; Smith, V. (2010). \"Report on trial of SatScan tray scanner system by SmartDrive Ltd.\". Nature Precedings: 7. http:\/\/precedings.nature.com\/documents\/4486\/version\/1 .   \n\n\u2191 Mantle, B.L.; La Salle, J.; Fisher, N. (2012). \"Whole-drawer imaging for digital management and curation of a large entomological collection\". ZooKeys 209: 147\u2013163. doi:10.3897\/zookeys.209.3169.   \n\n\u2191 11.0 11.1 Bertone, M.A.; Blinn, R.L.; Stanfield, T.M. et al. (2012). \"Results and insights from the NCSU Insect Museum GigaPan project\". ZooKeys 209: 115\u2013132. doi:10.3897\/zookeys.209.3083.   \n\n\u2191 Longson, J.; Cooper, G.; Gibson, R. et al. (2010). \"Adapting Traditional Macro and Micro Photography for Scientific Gigapixel Imaging\". Proceedings of the Fine International Conference on Gigapixel Imaging for Science. http:\/\/repository.cmu.edu\/gigapixel\/1\/ .   \n\n\u2191 13.0 13.1 Schmidt, S.; Balke, M.; Lafogler, S. (2012). \"DScan \u2013 a high-performance digital scanning system for entomological collections\". ZooKeys 209: 183\u2013191. doi:10.3897\/zookeys.209.3115.   \n\n\u2191 Dietrich, C.H.; Hart, J.; Raila, D. (2012). \"InvertNet: a new paradigm for digital access to invertebrate collections\". ZooKeys 209: 165\u2013181. doi:10.3897\/zookeys.209.3571.   \n\n\nAppendix 1 \nAn example of XML output of Metadata Creator:\n\n\n<?xml version=\u201d1.0\u201d encoding=\u201dutf-8\u201d?>\n\n<Project xmlns:xsi=\u201dhttp:\/\/www.w3.org\/2001\/XMLSchema-instance\u201d xmlns:xsd=\u201dhttp:\/\/www.w3.org\/2001\/XMLSchema\u201d>\n\n<Templates>\n\n<key>BMNHID<\/key>\n\n<value>A unique identifier for the British Natural History Museum<\/value>\n\n<key>GlobalUniqueIdentifier<\/key>\n\n<value>A Uniform Resource Name (URN) as a unique identifier for the specimen or observation record. In the absence of a persistent global unique identifier, construct one in the form: [InstitutionCode]:[CollectionCode]: [CatalogNumber] Examples: 1) urn:lsid:nhm.ku.edu:Herps:32 2) FMNH:Mammal:145732<\/value>\n\n<key>DateLastModified<\/key>\n\n<value>The last date-time of publication when any of the data for the record were modified from the previous publication of that record. When publishing a record for the first time, use the publication date-time. Returns values as ISO 8601 date and time<\/value>\n\n<key>BasisOfRecord<\/key>\n\n<value>A descriptive term indicating whether the record represents an object or observation.\n\n<\/value>\n\n<\/Templates>\n\n<Specimens>\n\n<Specimen>\n\n<DarwinCoreData>\n\n<key>ImageURL<\/key>\n\n<value>E:\\test\\T3\\specimens\\G1_2_0000.jpg<\/value>\n\n<key>BMNHID<\/key>\n\n<value> <\/value>\n\n<key>GlobalUniqueIdentifier<\/key>\n\n<value> <\/value>\n\n<key>DateLastModified<\/key>\n\n<value> <\/value>\n\n<key>BasisOfRecord<\/key>\n\n<value>preserved specimen<\/value>\n\n<\/DarwinCoreData>\n\n<SpecimenIndex>0<\/SpecimenIndex>\n\n<ImageDimensions>\n\n<Left>519.635599159075<\/Left>\n\n<Top>1490.562857142857<\/Top>\n\n<Width>2247.9887876664334<\/Width>\n\n<Height>3511.8564285714283<\/Height>\n\n<\/ImageDimensions>\n\n<\/Specimen>\n\n<Specimen>\n\n\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\n\n<\/Specimen>\n\n<\/Specimens>\n\n<\/Project>\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. Additionally, a missing reference (Vollmar et al. 2010) was added.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\">https:\/\/www.limswiki.org\/index.php\/Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on biodiversity informatics\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 4 March 2016, at 01:40.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 3,305 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","5405bb942ce8b77cfcb5385454aa4c95_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_No_specimen_left_behind_Industrial_scale_digitization_of_natural_history_collections skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:No specimen left behind: Industrial scale digitization of natural history collections<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>Traditional approaches for digitizing natural history collections, which include both imaging and metadata capture, are both labour- and time-intensive. Mass-digitization can only be completed if the resource-intensive steps, such as specimen selection and databasing of associated <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" target=\"_blank\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a>, are minimized. Digitization of larger collections should employ an \u201cindustrial\u201d approach, using the principles of automation and crowd sourcing, with minimal initial metadata collection including a mandatory persistent identifier. A new workflow for the mass-digitization of natural history museum collections based on these principles, and using SatScan\u00ae tray scanning system, is described.\n<\/p><p><b>Keywords<\/b>: Digitization, imaging, specimen metadata, natural history collections, biodiversity informatics\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>Natural history collections are of immense scientific and cultural importance. Specimens in public museums and herbaria and their associated data represent a potentially vast repository of information on biodiversity, ecosystems and natural resources for the widest range of stakeholders, from governments and NGOs to schools and private individuals. Numerous examples of the uses to which biodiversity data derived from natural history collections have been put in research on evolution and genetics, nature conservation and resource management, public health and safety, and education are widely available (summarized in Chapman 2005, Baird 2010).<sup id=\"rdp-ebb-cite_ref-ChapmanUses05_1-0\" class=\"reference\"><a href=\"#cite_note-ChapmanUses05-1\" rel=\"external_link\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-BairdLev10_2-0\" class=\"reference\"><a href=\"#cite_note-BairdLev10-2\" rel=\"external_link\">[2]<\/a><\/sup> The universe of natural history collection data has been estimated to be between 1.2 and 2.1 \u00d7 109 units (specimens, lots and collections) (Ari\u00f1o 2010).<sup id=\"rdp-ebb-cite_ref-ArinoApp10_3-0\" class=\"reference\"><a href=\"#cite_note-ArinoApp10-3\" rel=\"external_link\">[3]<\/a><\/sup> To ensure efficient access, dissemination and exploitation of such an immense wealth of biodiversity relevant data, it is evident that a well-coordinated and streamlined approach to global digitization is required, in particular because it is absolutely essential for the scientific value of the generated data that the outputs (images, metadata, etc.) are linked together and also back to the original specimens via unique identifiers (uIDs).\n<\/p><p>In recent years, substantial efforts and resources have been invested into the digitization of natural history collections, with museums and herbaria routinely employing specimen level collection databases to replace older, paper-based card indexes and ledgers. In theory, this should make dissemination of specimen data through <a href=\"https:\/\/www.limswiki.org\/index.php\/Biodiversity_informatics\" title=\"Biodiversity informatics\" target=\"_blank\" class=\"wiki-link\" data-key=\"e1fc3c3cb12287ecf307f488d3cd2357\">biodiversity informatics<\/a> portals such as the Global Biodiversity Information Facility (GBIF; <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.gbif.org\/\" target=\"_blank\">http:\/\/www.gbif.org\/<\/a>) very simple and straightforward. However, the truth is that natural history collections are almost as far from complete digitization as they were 20 years ago. Ari\u00f1o (2010)<sup id=\"rdp-ebb-cite_ref-ArinoApp10_3-1\" class=\"reference\"><a href=\"#cite_note-ArinoApp10-3\" rel=\"external_link\">[3]<\/a><\/sup> estimated that no more than 3% of biological specimen data is web-accessible through GBIF, the largest source of biodiversity information. Consequently, there is neither a central database of collection holdings, nor a complete collection index available to users. The reason for this deficiency is partly the immense effort it would take to digitize the vast number of collections units involved (Vollmar et al. 2010).<sup id=\"rdp-ebb-cite_ref-VollmarNat10_4-0\" class=\"reference\"><a href=\"#cite_note-VollmarNat10-4\" rel=\"external_link\">[4]<\/a><\/sup> The cost of traditional digitization workflows is vast, both in financial and human terms. Our simple calculations have shown that complete databasing of the ~30 million insect specimens housed in the entomological collection of the Natural History Museum, London, would require 23 years of continuous work from the entire departmental staff to complete (65 people). Depending on the particular collections and curatorial practices used, estimates vary from US$0.50 to several dollars per specimen to capture full label data (Heidorn 2011).<sup id=\"rdp-ebb-cite_ref-HeidornBio11_5-0\" class=\"reference\"><a href=\"#cite_note-HeidornBio11-5\" rel=\"external_link\">[5]<\/a><\/sup> The cost of traditional imaging and databasing of every natural history object in all European museums was recently estimated as \u20ac73.44 per object (Poole 2010).<sup id=\"rdp-ebb-cite_ref-PooleTheCost10_6-0\" class=\"reference\"><a href=\"#cite_note-PooleTheCost10-6\" rel=\"external_link\">[6]<\/a><\/sup> Thus, the complete digitization of all natural history collections may cost as much as \u20ac150, 000 million, and take as long as 1,500 years.\n<\/p><p>The most common solution proposed to overcome the enormous cost of digitization is prioritization based on user demand (Berents et al. 2010).<sup id=\"rdp-ebb-cite_ref-BerentsTow10_7-0\" class=\"reference\"><a href=\"#cite_note-BerentsTow10-7\" rel=\"external_link\">[7]<\/a><\/sup> Currently, most digitization projects concentrate their efforts on obtaining high quality images of selected specimens accompanied by high quality data (e.g., comprehensive and expertly interpreted label information) rather than total collections coverage. Such specimen-centric digitization efforts are thus inevitably fragmented into numerous small-scale and labour-intensive projects that usually image single specimens, one at a time.\n<\/p><p>To solve the problem of cost, as well as the inherent fragmentation in collection based biodiversity informatics, new, industrial-scale approaches to digitization are clearly needed. The larger a digitization project becomes, the lower are the transaction costs and thus the lower is the cost per specimen. Such an industrial-scale process must necessarily fulfill certain standardized criteria if it is to be of use to and adopted by a wide spectrum of natural history collections:\n<\/p>\n<ul><li> As much as possible of the procedure must be automated, except when physical handling of specimens is necessary.<\/li><\/ul>\n<ul><li> The approach should, whenever possible, focus on \u201cwall-to-wall\u201d total digitization of entire collections, because it is faster to digitize an entire collection than to select individual specimens or drawers of particular interest.<\/li><\/ul>\n<ul><li> Complicated labour-intensive procedures must be divided into a series of separate, shorter steps, each with a distinct outcome. For example, preparation of specimens for imaging should be a separate step from the imaging itself; and unique specimen identifiers can be assigned simultaneously to all specimens in a drawer rather than individually and sequentially. Such a modularised process can then be more easily crowd-sourced among the professional and volunteer communities. Properly organized crowd-sourcing projects would be able to mobilise the efforts of thousands of enthusiasts around the world (Hill et al. 2012).<sup id=\"rdp-ebb-cite_ref-HillTheNotes12_8-0\" class=\"reference\"><a href=\"#cite_note-HillTheNotes12-8\" rel=\"external_link\">[8]<\/a><\/sup><\/li><\/ul>\n<ul><li> Collection of metadata must be simplified and standardized. In most cases, digital representation of the specimen and minimal metadata (uID, specimen location in the collection) is sufficient for collection management purposes. Only minimal information should be collected when initially digitizing an entire collection, but in such a way that it can be amended and expanded upon later.<\/li><\/ul>\n<p>Here we describe a new method for \u201cwall-to-wall\u201d mass-digitization of natural history museum collections based on the SatScan\u00ae tray scanning system. The method allows for standardized scanning of museum collection trays of the highest image quality possible, followed by simplified (and easily expandable) collection of metadata.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Methods\">Methods<\/span><\/h2>\n<p>The Natural History Museum (NHM), London, has been working with SmartDrive Limited (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.smartdrive.co.uk\/\" target=\"_blank\">http:\/\/www.smartdrive.co.uk\/<\/a>) since 2009 on the development of one of the company\u2019s products, the SatScan\u00ae collection scanner (Fig. 1). From this collaboration, we have developed a workflow that we consider meets our needs for the industrial-scale digitization of a significant part of the NHM\u2019s collections. The system is particularly suited to the digitization of multiple, uniformly mounted or laid out specimens, such as pinned insects and smaller geological or mineralogical objects in standardized collection drawers, horizontally-stored microscope slides and herbarium sheets.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_BlagoderovZooKeys2012_209.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"e6631c9f680daadbc3b28eea88c7b813\"><img alt=\"Fig1 BlagoderovZooKeys2012 209.jpg\" src=\"https:\/\/www.limswiki.org\/images\/4\/49\/Fig1_BlagoderovZooKeys2012_209.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 1.<\/b> SatScan imaging: a SatScan machine b specimens being imaged c individual frames aligned d fragment of a stitched image; final resolution of the stitched image ~11 lines\/mm<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>The digitization workflow envisioned for the NHM (Fig. 2) comprises three steps:\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_BlagoderovZooKeys2012_209.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"efd578cd18b36a5caf8355a0fd24b484\"><img alt=\"Fig2 BlagoderovZooKeys2012 209.jpg\" src=\"https:\/\/www.limswiki.org\/images\/5\/50\/Fig2_BlagoderovZooKeys2012_209.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 2.<\/b> Image based digitization workflow consisting of four stages: Imaging, Metadata capture, Institutional databasing and Publication<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h3><span class=\"mw-headline\" id=\"Imaging\">Imaging<\/span><\/h3>\n<p>The SatScan\u00ae collection scanner is capable of producing high-resolution images of entire collection drawers (see Table 1, Blagoderov et al. 2010, Mantle et al. 2012).<sup id=\"rdp-ebb-cite_ref-BlagoderovRep10_9-0\" class=\"reference\"><a href=\"#cite_note-BlagoderovRep10-9\" rel=\"external_link\">[9]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-MantleWhole12_10-0\" class=\"reference\"><a href=\"#cite_note-MantleWhole12-10\" rel=\"external_link\">[10]<\/a><\/sup> The specific configuration of the system has changed somewhat from that described in the report, such that now a USB CMOS UEye-SE camera (model # UI-1480SE-C-HQ, 2560\u00d71920 resolution) is used in combination with Edmund Optics telecentric TML lenses of 0.3\u00d7 (#58428) and 0.16\u00d7 TML (#56675). A camera with attached lens is moved in two dimensions along precision-engineered rails positioned above the object to be imaged. A combination of hardware and software provides automated capture of high resolution images of small regions of interest, which are then assembled (\u201cstitched\u201d) into a larger panoramic image, generating the final image of the entire drawer. This method maximizes depth of field of the captured images and minimizes distortion and parallax artefacts. Analogous solutions for large-area imaging which have been developed independently include GigaPan (Bertone et al. 2012)<sup id=\"rdp-ebb-cite_ref-BertoneRes12_11-0\" class=\"reference\"><a href=\"#cite_note-BertoneRes12-11\" rel=\"external_link\">[11]<\/a><\/sup>, MicroGigaPan (Longson et al. 2010)<sup id=\"rdp-ebb-cite_ref-LongsonAdapt10_12-0\" class=\"reference\"><a href=\"#cite_note-LongsonAdapt10-12\" rel=\"external_link\">[12]<\/a><\/sup> and DScan (Schmidt et al. 2012).<sup id=\"rdp-ebb-cite_ref-SchmidtDS12_13-0\" class=\"reference\"><a href=\"#cite_note-SchmidtDS12-13\" rel=\"external_link\">[13]<\/a><\/sup>\n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" colspan=\"7\"><b>Table 1.<\/b> Resolution and depth of field of the system as compared with a Canon EOS450D DSLR camera using a Canon MP E-65 macrolens (USAF: the smallest resolvable element on 1951 US Air Force resolution test chart; MRD: minimal resolved distance, size of the smallest visible object on image)\n<\/td><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\" rowspan=\"2\">Objective\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\" rowspan=\"2\">Sensor Resolution\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\" rowspan=\"2\">Aperture\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\" rowspan=\"2\">Depth of Field, mm\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\" colspan=\"3\">Resolution\n<\/th><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">USAF\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Lines, mm\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">MRD, \u03bcm\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" rowspan=\"6\">SatScan 0.16\u00d7 lens\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" rowspan=\"3\">1280\u00d7960\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Open\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3\u20134\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">44\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Dot\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">10\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3\u20134\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">44\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Closed\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">>70\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2\u20135\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">6.35\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">79\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" rowspan=\"3\">2560\u00d71920\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Open\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4\u20133\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">20.16\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">25\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Dot\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">14\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4\u20131\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">16.0\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">31\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Closed\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">>70\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3\u20132\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8.89\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">56\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" rowspan=\"6\">SatScan 0.3\u00d7 lens\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" rowspan=\"3\">1280\u00d7960\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Open\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4\u20132\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">17.95\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">28\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Dot\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4.5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4\u20132\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">17.95\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">28\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Closed\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">30\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3\u20134\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">44\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" rowspan=\"3\">2560\u00d71920\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Open\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1.5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5\u20133\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">40.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">12\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Dot\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5\u20132\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">36.0\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">14\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Closed\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">35\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3\u20135\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">12.7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">39\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" rowspan=\"2\">Canon MP-E65 lens, 1\u00d7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" rowspan=\"2\">4272\u00d72848\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.8\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5\u20136\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">57\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8.8\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">16\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" rowspan=\"2\">Canon MP-E65 lens, 5\u00d7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" rowspan=\"2\">4272\u00d72848\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.8\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><0.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8\u20131\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">256\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">16\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">6\u20132\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">71.8\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h3><span class=\"mw-headline\" id=\"Metadata_capture\">Metadata capture<\/span><\/h3>\n<p>A prototype software program, Metadata Creator, has been designed to allow fast capture of specimen data and associating these with the image of the specimen (Fig. 3). Users can mark individual specimens on the panoramic image by drawing rectangular boxes around them, selecting these areas and annotating them individually or in batches. Methods for marking the specimen, editing regions of interest and selection of multiple specimens are analogous to those used in many common graphic applications and so will be familiar, even to inexperienced users.\n<\/p><p>Specimen metadata is captured in a series of fields that are compatible with the Darwin Core 1.4.1 schema (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/rs.tdwg.org\/dwc\/\" target=\"_blank\">http:\/\/rs.tdwg.org\/dwc\/<\/a>) and which can be customized to particular user requirements. To maximize throughput, only basic metadata are collected at this stage. These will generally include a unique collection number of every specimen (see below, barcodes), collection identification (to the available curatorial level, e.g. to species\/subspecies for the \u201cMain Collection\u201d and family\/order for unsorted accessions), and, if possible, biogeographic region\/country. Taxon names are looked up from an index derived from the NHM Collections Management Database. A completed project comprises a folder with an archival image of the drawer, full-resolution images of individual specimens cut-out from the drawer image, and an XML file containing annotations and links to specimen images (Appendix 1). Trials have demonstrated that 10\u201320 seconds per specimen is required to capture basic metadata using the Metadata Creator Software. A unique ID for the drawer is also recorded. As the NHM Collection Management System already includes a complete collections index (a brief description of the content of every drawer), no additional information is required.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_BlagoderovZooKeys2012_209.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"f41637f8f0720101b7851ce1eadefe11\"><img alt=\"Fig3 BlagoderovZooKeys2012 209.jpg\" src=\"https:\/\/www.limswiki.org\/images\/a\/a6\/Fig3_BlagoderovZooKeys2012_209.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 3.<\/b> Metadata Creator software: <b>a\u2013c<\/b> working areas <b>a<\/b> drawer image <b>b<\/b> specimen records <b>c<\/b> annotation fields <b>d<\/b> tool selector <b>e<\/b> unique IDs<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h3><span class=\"mw-headline\" id=\"Assigning_uIDs\">Assigning uIDs<\/span><\/h3>\n<p>Every specimen is assigned a unique number under which it will be registered in the NHM Collections Management Database. It is a requirement of collections management procedures that a label bearing the specimen\u2019s uID is attached to the specimen. To streamline this part of the process, it is subdivided into the following steps:\n<\/p>\n<ol><li> A sequence of unique numbers is generated from the NHM Collections Management Database.<\/li>\n<li> Labels that include both a human-readable number and a machine-readable barcode are printed.<\/li>\n<li> The operator labels the specimens by selecting a specimen on the drawer image, pinning a label under the specimen, and scanning the barcode, thereby adding the uID into the corresponding field of Metadata Creator. Barcodes can be pinned facing up or down depending on curatorial practice; the former has the advantage of visibility on the image. In this case imaging, of course, has to take place after assigning uIDs. Images of individual specimens for which the metadata have been collected and individual numbers assigned are automatically marked on the drawer image with a grey spot, allowing easy visualization of progress.<\/li>\n<li> When all specimens have been labelled and recorded, the XML file and corresponding specimen images are imported into the NHM Collections Management Database.<\/li><\/ol>\n<p>We must emphasize that Metadata Creator is a prototype software application; much more development is needed for to perfect its functionality, user interface, and integration with the Museum\u2019s information systems.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h2>\n<p>A preliminary assessment of the SatScan\u00ae system was undertaken and reported upon by Blagoderov et al. (2010).<sup id=\"rdp-ebb-cite_ref-BlagoderovRep10_9-1\" class=\"reference\"><a href=\"#cite_note-BlagoderovRep10-9\" rel=\"external_link\">[9]<\/a><\/sup> Based on their findings, a series of recommendations were made for improvements and possible longer term developments to the hardware, software, imaging system and ergonomics. An updated system was delivered to the NHM in September 2011 and further trials were then conducted. This newer version of SatScan\u00ae provides non-extrapolated resolution of the final images from 11.3 to 40.3 lines\/mm and a minimum resolved distance of 79 to 12\u03bcm, depending on the lens and sensor settings employed (Table 1). The maximum depth of field has been increased slightly from 80mm to 85mm. Although focus stacking is implemented in the current version of the system, in most cases it is not necessary. For the majority of collections drawers, specimens are presented at a more-or-less uniform height and within the available depth of field; focus stacking is really only necessary for those drawers where specimens are pinned at markedly different heights or are particularly deep (e.g. fossils and mineralogical samples). The average time to scan a typical collection drawer without focus stacking is between four and six minutes, depending upon size (eight to ten minutes including logistics, Table 2). This generally translates to about two seconds per specimen. Thus, in a working day, an operator could image up to 70 drawers. These would then be stitched into the final images using an overnight batch process (see average figures in Table 2). The resulting images vary in size from 0.3 Gpx to 5 Gpx (109 pixels; 250 MB \u2013 3 GB compressed TIFF files) depending on the imaging area, lens and resolution used. However, use of the highest resolution in mass digitization projects may not always be practical. We did not conduct extensive tests with the highest resolution of camera\/higher magnification of lens because a 64-bit version of software is needed to handle the stitching process for files of this size, and this was not available at the time of trials.\n<\/p><p>The part of the process that involves marking of specimens and metadata capture using Metadata Creator has not been as thoroughly tested and we have yet to trial the part of the procedure that produces barcode labels and attaches these to specimens. However, preliminary results involving mock elements indicate that it will take about ten seconds per specimen. This time will be extended for those specimens that already have a human-readable uID (a \u201cBMNH(E)\u201d number, for example) but no barcode label, because then the former will have to be manually entered into Metadata Creator and a new barcode label printed. However, relatively few NHM insect specimens (about 1.2%) have so far been databased and assigned a uID.\n<\/p><p>The entomology collections of the NHM have about 30 million insect specimens, mostly pinned, housed in 135, 000 collections drawers. Assuming that 80% of the collection is appropriate to be imaged using the SatScan\u00ae system, rough calculations based on the above figures suggest that the entire collection could be imaged and basic metadata captured in 18 person-years.\n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" colspan=\"7\"><b>Table 2.<\/b> Scanning and stitching times for different types of drawers\n<\/td><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">Drawer type\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Number of drawers in trials\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Dimensions, mm\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Number of frames\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Average scanning time (including logistics), min\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Average stitching time, min\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">File size, Mb\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Main collection and accessions\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">236\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">500\u00d7400 or 470\u00d7450\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">17\u00d714 or 16\u00d715\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8.52\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">12.65\u00b11.54\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">488.20\u00b130.21\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Rothschild and Rhopalocera\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">144\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">560x540 or 570x 555\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">21\u00d717 or 22\u00d717\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">10.13\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">25.41\u00b14.21\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">715.90\u00b189.58\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h2><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h2>\n<p>Although images acquired through an industrial digitization process might be considered to be of limited use for taxonomic purposes, because they feature only one aspect of the specimens and may not contain necessary morphological details or label data, they could prove very useful for a variety of other purposes. Obvious collection management applications include improved collection audit and security, as well as improving accessibility of the collection. For research purposes, such acquired images could prove very valuable in morphometric analyses and phenological population studies. In addition, the public engagement aspect of industrial digitization activities should not be underestimated. Online public access to high resolution images and metadata will likely enhance public awareness of the importance of local and national collections (as well as engendering a sense of shared ownership). Moreover, high quality images will open up the possibility for fast and reliable automated or semi-automated specimen identification and thus encourage environmental \u201ccitizen-science\u201d, such as recording distributional or abundance changes of key species.\n<\/p><p>Major problems remaining with the described approach are largely concerned with the time taken to scan specimens\/samples and to collect metadata. Even with a simple approach, scanning a specimen takes approximately two to four seconds followed by 10\u201320s for annotation and\/or barcoding. Furthermore, only basic metadata are collected under the scenario described above. Indeed, in the worst case, say a drawer of unidentified mixed organisms from several phyla, only a uID will be associated with each of the specimens. It may then be argued that this will compel museums and herbaria to create essentially incomplete records with which to populate their collection databases. However, such records are comparable to stub pages in Wikipedia, empty at the moment but capable of being filled and edited in due course. Indeed, there is a case to be made for the opposite viewpoint, that there is no point collecting complete metadata if these are not going to be used for any purpose. Finally, it should be noted that the industrial digitization process described above only works relatively seamlessly for more-or-less uniformly preserved and presented specimens, such pinned insects in drawers and herbarium sheets. It is unlikely to be satisfactory for pickled specimens in jars of ethanol. These collections may have to be digitized using a different protocol.\n<\/p><p>Approximately 90% of the time required for digitization is spent on capturing metadata and labelling specimens. While the latter involves physical handling of the specimens and must be performed by experienced staff, selection of specimens in the drawer images and annotation thereof can be undertaken in a virtual environment. In many cases, the basic information to be collected can be seen in the drawer image. Implementing an open source web application that duplicates the functions of Metadata Creator and publication of drawer images using algorithms involving a pyramid of tiles (produced using Zoomify\u2122 (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.zoomify.com\/\" target=\"_blank\">http:\/\/www.zoomify.com\/<\/a>) or Google Maps (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/maps.google.com\/\" target=\"_blank\">http:\/\/maps.google.com\/<\/a>), for example) will allow volunteers from around the world to participate in digitization of the collection and will decrease the time needed to process a specimen by at least 50%.\n<\/p><p>The next step in facilitating the digitization process might be to undertake \u201cvirtual curation\u201d. Here, uIDs are assigned to each specimen, records are created in the collection management database and corresponding specimen images linked to these records, but the specimens themselves are not labelled until it becomes necessary to handle the specimen physically for some other purpose (curation, loan, identification, dissection, etc.). Of course, these procedural changes would require a major cultural shift for Collections Management staff.\n<\/p><p>Revised, though still simplistic, calculations now show that the entire NHM collection of insects could be imaged in 12.88 person-years and completely digitized without crowd-sourcing in 118 person-years. Collecting basic information and attaching a barcode to a specimen would take approximately 10-30 seconds. Per-specimen cost under the current (2012) economic climate would thus be as low as \u00a30.12. If we limit SatScan-based digitization to large and medium-size insects (up to 5 mm in length), the total time required is 58 man-years. This effort does not seem insuperable considering that the NHM insect collection is managed by 26 permanent curatorial staff, assisted by a number of people in short-term contracts and volunteers.\n<\/p><p>Despite the potential perceived drawbacks, image-based basic digitization can nevertheless mobilize hundreds of millions of biological specimens in a relatively short period of time. It is estimated that entomological specimens constitute up to 40% of all natural history specimens (Ari\u00f1o 2010).<sup id=\"rdp-ebb-cite_ref-ArinoApp10_3-2\" class=\"reference\"><a href=\"#cite_note-ArinoApp10-3\" rel=\"external_link\">[3]<\/a><\/sup> Some palaeontological, zoological and mineralogical specimens, including microscopic slides, are also stored in collection drawers and trays that are amenable to simultaneous imaging. Thus, the majority of natural history specimens could potentially be digitized using industrial imaging.\n<\/p><p>The return on investment in total collection digitization will be enormous. It will open up collections to the world, facilitating their use, and help create a global collection index that can be used to set priorities for further digitization. Basic digitization of all the world\u2019s holdings of insects (800 million specimens) could be completed in less than 4000 person-years. This may sound like a huge figure, but divided among approximately 1, 300 collections and potentially tens of thousands of professionals and volunteers, the work could be completed much quicker, perhaps in only a few years. \"Furthermore, emerging technologies in the near future will undoubtedly decrease time and costs, while increasing data quality. Complete image-based basic digitization of insect and plant collections would produce at least 30 Pb (1015 bytes) of data, which constitutes ~0.0006% of the current data hosted on the Internet. At \u00a30.2 per specimen, the cost of digitizing 2, 000 million natural history specimens may appear to be an eye-wateringly high figure of \u00a3400 million. However, divided among ~4, 000 natural history collections, this reduces to an average project cost of \u00a3100, 000, which is equivalent to the size of a relatively modest research grant. To this the cost of imaging equipment must be added. At present, a SatScan system costs between \u00a325, 000 and \u00a360, 000, depending on the options to be implemented and the service agreement chosen, but less expensive alternative solutions are also being developed (Bertone et al. 2012, Dietrich et al. 2012, Schmidt et al. 2012).<sup id=\"rdp-ebb-cite_ref-BertoneRes12_11-1\" class=\"reference\"><a href=\"#cite_note-BertoneRes12-11\" rel=\"external_link\">[11]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-DietrichInv12_14-0\" class=\"reference\"><a href=\"#cite_note-DietrichInv12-14\" rel=\"external_link\">[14]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-SchmidtDS12_13-1\" class=\"reference\"><a href=\"#cite_note-SchmidtDS12-13\" rel=\"external_link\">[13]<\/a><\/sup>\n<\/p><p>Regardless of the technology used, mass digitization will nevertheless follow the same general approach, which includes mechanisms that enrich digital media with specimen-level metadata. This enrichment will:\n<\/p>\n<ol><li> Facilitate open dissemination of data so that it can be discovered and accessed by stakeholders, reducing both the need for physical access to collections and the number of loans;<\/li>\n<li> Enable large-scale manipulation and integration of collection data, supporting stakeholders in their monitoring and management of information on ecosystems, biodiversity and natural resources;<\/li>\n<li> Enhance curatorial activities, allowing the condition of loans to be tracked and reduce identification inaccuracies;<\/li>\n<li> Protect biodiversity heritage by reducing the need to handle irreplaceable specimens;<\/li>\n<li> Improve collections security by providing base-line images against which damage and thefts can be monitored;<\/li>\n<li> Support disaster management, such that should the worst happen to a collection, its digital representation will continue to provide a valuable resource;<\/li>\n<li> Raise natural history collections profiles, resulting in improved resources for further research;<\/li>\n<li> Contribute beyond the traditional remit of museums and herbaria into new areas of interest, particularly education and public understanding of science; and<\/li>\n<li> Support biodiversity legislation and data repatriation, which is an increasing requirement under both the 1992 Convention on Biological Diversity and the subsequent 2010 Nagoya Protocol on Access and Benefit-sharing.<\/li><\/ol>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>The authors are very grateful to Dennis Murphy, Dave Freer, and Mike Broderick (SmartDrive Ltd.) for fruitful and ongoing collaboration; Chris Raper for help with testing the system and development of software; and two reviewers, in particular Matt Yoder, whose comments and suggestions greatly improved original version of the manuscript.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<ol class=\"references\">\n<li id=\"cite_note-ChapmanUses05-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-ChapmanUses05_1-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Chapman, A. 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(2011). \"Biodiversity informatics\". <i>Bulletin of the American Society for Information Science and Technology<\/i> <b>37<\/b> (6): 38\u201344. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fbult.2011.1720370612\" target=\"_blank\">10.1002\/bult.2011.1720370612<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Biodiversity+informatics&rft.jtitle=Bulletin+of+the+American+Society+for+Information+Science+and+Technology&rft.aulast=Heidorn%2C+P.B.&rft.au=Heidorn%2C+P.B.&rft.date=2011&rft.volume=37&rft.issue=6&rft.pages=38%E2%80%9344&rft_id=info:doi\/10.1002%2Fbult.2011.1720370612&rfr_id=info:sid\/en.wikipedia.org:Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-PooleTheCost10-6\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-PooleTheCost10_6-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Poole, N. 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(2010). \"Towards demand driven publishing: Approches to the prioritisation of digitisation of natural history collections data\". <i>Biodiversity Informatics<\/i> <b>7<\/b> (2): 113\u2013119. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.17161%2Fbi.v7i2.3990\" target=\"_blank\">10.17161\/bi.v7i2.3990<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Towards+demand+driven+publishing%3A+Approches+to+the+prioritisation+of+digitisation+of+natural+history+collections+data&rft.jtitle=Biodiversity+Informatics&rft.aulast=Berents%2C+P.%3B+Hamer%2C+M.%3B+Chavan%2C+V.&rft.au=Berents%2C+P.%3B+Hamer%2C+M.%3B+Chavan%2C+V.&rft.date=2010&rft.volume=7&rft.issue=2&rft.pages=113%E2%80%93119&rft_id=info:doi\/10.17161%2Fbi.v7i2.3990&rfr_id=info:sid\/en.wikipedia.org:Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-HillTheNotes12-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-HillTheNotes12_8-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hill, A.; Guralnick, R.; Smith, A. (2012). \"The notes from nature tool for unlocking biodiversity records from museum records through citizen science\". <i>ZooKeys<\/i> <b>209<\/b>: 219\u2013233. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3897%2Fzookeys.209.3472\" target=\"_blank\">10.3897\/zookeys.209.3472<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+notes+from+nature+tool+for+unlocking+biodiversity+records+from+museum+records+through+citizen+science&rft.jtitle=ZooKeys&rft.aulast=Hill%2C+A.%3B+Guralnick%2C+R.%3B+Smith%2C+A.&rft.au=Hill%2C+A.%3B+Guralnick%2C+R.%3B+Smith%2C+A.&rft.date=2012&rft.volume=209&rft.pages=219%E2%80%93233&rft_id=info:doi\/10.3897%2Fzookeys.209.3472&rfr_id=info:sid\/en.wikipedia.org:Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-BlagoderovRep10-9\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-BlagoderovRep10_9-0\" rel=\"external_link\">9.0<\/a><\/sup> <sup><a href=\"#cite_ref-BlagoderovRep10_9-1\" rel=\"external_link\">9.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Blagoderov, V.; Kitching, I.; Simonsen, T.; Smith, V. (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/precedings.nature.com\/documents\/4486\/version\/1\" target=\"_blank\">\"Report on trial of SatScan tray scanner system by SmartDrive Ltd.\"<\/a>. <i>Nature Precedings<\/i>: 7<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/precedings.nature.com\/documents\/4486\/version\/1\" target=\"_blank\">http:\/\/precedings.nature.com\/documents\/4486\/version\/1<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Report+on+trial+of+SatScan+tray+scanner+system+by+SmartDrive+Ltd.&rft.jtitle=Nature+Precedings&rft.aulast=Blagoderov%2C+V.%3B+Kitching%2C+I.%3B+Simonsen%2C+T.%3B+Smith%2C+V.&rft.au=Blagoderov%2C+V.%3B+Kitching%2C+I.%3B+Simonsen%2C+T.%3B+Smith%2C+V.&rft.date=2010&rft.pages=7&rft_id=http%3A%2F%2Fprecedings.nature.com%2Fdocuments%2F4486%2Fversion%2F1&rfr_id=info:sid\/en.wikipedia.org:Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-MantleWhole12-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-MantleWhole12_10-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mantle, B.L.; La Salle, J.; Fisher, N. (2012). \"Whole-drawer imaging for digital management and curation of a large entomological collection\". <i>ZooKeys<\/i> <b>209<\/b>: 147\u2013163. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3897%2Fzookeys.209.3169\" target=\"_blank\">10.3897\/zookeys.209.3169<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Whole-drawer+imaging+for+digital+management+and+curation+of+a+large+entomological+collection&rft.jtitle=ZooKeys&rft.aulast=Mantle%2C+B.L.%3B+La+Salle%2C+J.%3B+Fisher%2C+N.&rft.au=Mantle%2C+B.L.%3B+La+Salle%2C+J.%3B+Fisher%2C+N.&rft.date=2012&rft.volume=209&rft.pages=147%E2%80%93163&rft_id=info:doi\/10.3897%2Fzookeys.209.3169&rfr_id=info:sid\/en.wikipedia.org:Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-BertoneRes12-11\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-BertoneRes12_11-0\" rel=\"external_link\">11.0<\/a><\/sup> <sup><a href=\"#cite_ref-BertoneRes12_11-1\" rel=\"external_link\">11.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bertone, M.A.; Blinn, R.L.; Stanfield, T.M. et al. (2012). \"Results and insights from the NCSU Insect Museum GigaPan project\". <i>ZooKeys<\/i> <b>209<\/b>: 115\u2013132. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3897%2Fzookeys.209.3083\" target=\"_blank\">10.3897\/zookeys.209.3083<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Results+and+insights+from+the+NCSU+Insect+Museum+GigaPan+project&rft.jtitle=ZooKeys&rft.aulast=Bertone%2C+M.A.%3B+Blinn%2C+R.L.%3B+Stanfield%2C+T.M.+et+al.&rft.au=Bertone%2C+M.A.%3B+Blinn%2C+R.L.%3B+Stanfield%2C+T.M.+et+al.&rft.date=2012&rft.volume=209&rft.pages=115%E2%80%93132&rft_id=info:doi\/10.3897%2Fzookeys.209.3083&rfr_id=info:sid\/en.wikipedia.org:Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LongsonAdapt10-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-LongsonAdapt10_12-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Longson, J.; Cooper, G.; Gibson, R. et al. (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/repository.cmu.edu\/gigapixel\/1\/\" target=\"_blank\">\"Adapting Traditional Macro and Micro Photography for Scientific Gigapixel Imaging\"<\/a>. <i>Proceedings of the Fine International Conference on Gigapixel Imaging for Science<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/repository.cmu.edu\/gigapixel\/1\/\" target=\"_blank\">http:\/\/repository.cmu.edu\/gigapixel\/1\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Adapting+Traditional+Macro+and+Micro+Photography+for+Scientific+Gigapixel+Imaging&rft.jtitle=Proceedings+of+the+Fine+International+Conference+on+Gigapixel+Imaging+for+Science&rft.aulast=Longson%2C+J.%3B+Cooper%2C+G.%3B+Gibson%2C+R.+et+al.&rft.au=Longson%2C+J.%3B+Cooper%2C+G.%3B+Gibson%2C+R.+et+al.&rft.date=2010&rft_id=http%3A%2F%2Frepository.cmu.edu%2Fgigapixel%2F1%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SchmidtDS12-13\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-SchmidtDS12_13-0\" rel=\"external_link\">13.0<\/a><\/sup> <sup><a href=\"#cite_ref-SchmidtDS12_13-1\" rel=\"external_link\">13.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Schmidt, S.; Balke, M.; Lafogler, S. (2012). \"DScan \u2013 a high-performance digital scanning system for entomological collections\". <i>ZooKeys<\/i> <b>209<\/b>: 183\u2013191. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3897%2Fzookeys.209.3115\" target=\"_blank\">10.3897\/zookeys.209.3115<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=DScan+%E2%80%93+a+high-performance+digital+scanning+system+for+entomological+collections&rft.jtitle=ZooKeys&rft.aulast=Schmidt%2C+S.%3B+Balke%2C+M.%3B+Lafogler%2C+S.&rft.au=Schmidt%2C+S.%3B+Balke%2C+M.%3B+Lafogler%2C+S.&rft.date=2012&rft.volume=209&rft.pages=183%E2%80%93191&rft_id=info:doi\/10.3897%2Fzookeys.209.3115&rfr_id=info:sid\/en.wikipedia.org:Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-DietrichInv12-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-DietrichInv12_14-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Dietrich, C.H.; Hart, J.; Raila, D. (2012). \"InvertNet: a new paradigm for digital access to invertebrate collections\". <i>ZooKeys<\/i> <b>209<\/b>: 165\u2013181. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3897%2Fzookeys.209.3571\" target=\"_blank\">10.3897\/zookeys.209.3571<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=InvertNet%3A+a+new+paradigm+for+digital+access+to+invertebrate+collections&rft.jtitle=ZooKeys&rft.aulast=Dietrich%2C+C.H.%3B+Hart%2C+J.%3B+Raila%2C+D.&rft.au=Dietrich%2C+C.H.%3B+Hart%2C+J.%3B+Raila%2C+D.&rft.date=2012&rft.volume=209&rft.pages=165%E2%80%93181&rft_id=info:doi\/10.3897%2Fzookeys.209.3571&rfr_id=info:sid\/en.wikipedia.org:Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Appendix_1\">Appendix 1<\/span><\/h2>\n<p>An example of XML output of Metadata Creator:\n<\/p>\n<pre>\n<?xml version=\u201d1.0\u201d encoding=\u201dutf-8\u201d?>\n\n<Project xmlns:xsi=\u201dhttp:\/\/www.w3.org\/2001\/XMLSchema-instance\u201d xmlns:xsd=\u201dhttp:\/\/www.w3.org\/2001\/XMLSchema\u201d>\n\n<Templates>\n\n<key>BMNHID<\/key>\n\n<value>A unique identifier for the British Natural History Museum<\/value>\n\n<key>GlobalUniqueIdentifier<\/key>\n\n<value>A Uniform Resource Name (URN) as a unique identifier for the specimen or observation record. In the absence of a persistent global unique identifier, construct one in the form: [InstitutionCode]:[CollectionCode]: [CatalogNumber] Examples: 1) urn:lsid:nhm.ku.edu:Herps:32 2) FMNH:Mammal:145732<\/value>\n\n<key>DateLastModified<\/key>\n\n<value>The last date-time of publication when any of the data for the record were modified from the previous publication of that record. When publishing a record for the first time, use the publication date-time. Returns values as ISO 8601 date and time<\/value>\n\n<key>BasisOfRecord<\/key>\n\n<value>A descriptive term indicating whether the record represents an object or observation.\n\n<\/value>\n\n<\/Templates>\n\n<Specimens>\n\n<Specimen>\n\n<DarwinCoreData>\n\n<key>ImageURL<\/key>\n\n<value>E:\\test\\T3\\specimens\\G1_2_0000.jpg<\/value>\n\n<key>BMNHID<\/key>\n\n<value> <\/value>\n\n<key>GlobalUniqueIdentifier<\/key>\n\n<value> <\/value>\n\n<key>DateLastModified<\/key>\n\n<value> <\/value>\n\n<key>BasisOfRecord<\/key>\n\n<value>preserved specimen<\/value>\n\n<\/DarwinCoreData>\n\n<SpecimenIndex>0<\/SpecimenIndex>\n\n<ImageDimensions>\n\n<Left>519.635599159075<\/Left>\n\n<Top>1490.562857142857<\/Top>\n\n<Width>2247.9887876664334<\/Width>\n\n<Height>3511.8564285714283<\/Height>\n\n<\/ImageDimensions>\n\n<\/Specimen>\n\n<Specimen>\n\n\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\n\n<\/Specimen>\n\n<\/Specimens>\n\n<\/Project>\n<\/pre>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. Additionally, a missing reference (Vollmar et al. 2010) was added.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192208\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.378 seconds\nReal time usage: 0.403 seconds\nPreprocessor visited node count: 11725\/1000000\nPreprocessor generated node count: 30975\/1000000\nPost\u2010expand include size: 74384\/2097152 bytes\nTemplate argument size: 23655\/2097152 bytes\nHighest expansion depth: 15\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 367.485 1 - -total\n 76.82% 282.288 1 - Template:Reflist\n 64.47% 236.915 14 - Template:Citation\/core\n 56.60% 207.985 12 - Template:Cite_journal\n 16.84% 61.874 1 - Template:Infobox_journal_article\n 16.22% 59.620 1 - Template:Infobox\n 12.58% 46.220 2 - Template:Cite_web\n 9.80% 36.012 80 - Template:Infobox\/row\n 4.94% 18.151 10 - Template:Citation\/identifier\n 3.20% 11.751 15 - Template:Citation\/make_link\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:8236-0!*!0!!en!5!* and timestamp 20181214192208 and revision id 24435\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections\">https:\/\/www.limswiki.org\/index.php\/Journal:No_specimen_left_behind:_Industrial_scale_digitization_of_natural_history_collections<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","5405bb942ce8b77cfcb5385454aa4c95_images":["https:\/\/www.limswiki.org\/images\/4\/49\/Fig1_BlagoderovZooKeys2012_209.jpg","https:\/\/www.limswiki.org\/images\/5\/50\/Fig2_BlagoderovZooKeys2012_209.jpg","https:\/\/www.limswiki.org\/images\/a\/a6\/Fig3_BlagoderovZooKeys2012_209.jpg"],"5405bb942ce8b77cfcb5385454aa4c95_timestamp":1544815327,"241f9c1d4812074890e77322c80e615c_type":"article","241f9c1d4812074890e77322c80e615c_title":"Efficient sample tracking with OpenLabFramework (List et al. 2014)","241f9c1d4812074890e77322c80e615c_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Efficient_sample_tracking_with_OpenLabFramework","241f9c1d4812074890e77322c80e615c_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:Efficient sample tracking with OpenLabFramework\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nEfficient sample tracking with OpenLabFrameworkJournal\n \nScientific ReportsAuthor(s)\n \nList, Markus; Schmidt, Steffen; Trojnar, Jakub; Thomas, Jochen; Thomassen, Mads; Kruse, Torben A.; Tan, Qihua; Baumbach, Jan; Mollenhauer, JanAuthor affiliation(s)\n \nUniversity of Southern Denmark, io-consultants GmbH & Co. KGPrimary contact\n \nEmail: http:\/\/www.nature.com\/articles\/srep04278\/email\/correspondent\/c1\/new (Requires login)Year published\n \n2014Volume and issue\n \n4Page(s)\n \n4278DOI\n \n10.1038\/srep04278ISSN\n \n2045-2322Distribution license\n \nCreative Commons Attribution-NonCommercial-ShareAlike 3.0 UnportedWebsite\n \nhttp:\/\/www.nature.com\/articles\/srep04278Download\n \nhttp:\/\/www.nature.com\/articles\/srep04278.pdf (PDF)\n\nContents\n\n1 Abstract \n2 Introduction \n3 Results \n\n3.1 Implementation \n3.2 Data handling \n3.3 Flexibility in deployment \n3.4 User acceptance and excess value \n3.5 Security \n3.6 OpenLabFramework \n\n3.6.1 Modularity and extendibility \n3.6.2 Reporting \n3.6.3 Flexibility \n3.6.4 Cloud deployment \n3.6.5 Mobile support \n3.6.6 User approachability and excess value \n3.6.7 Example for practical implementation and user acceptance - OLF at the NanoCAN Center \n3.6.8 Recommended system configuration \n\n\n\n\n4 Methods \n\n4.1 Grails web-application framework \n4.2 OpenLabFramework \n\n\n5 Discussion \n6 Conclusions \n7 Additional information \n\n7.1 Availability and Requirements \n\n\n8 Acknowledgements \n9 Author information \n\n9.1 Affiliations \n9.2 Contributions \n9.3 Competing interests \n9.4 Corresponding author \n\n\n10 Supplementary information \n11 References \n12 Notes \n\n\n\nAbstract \nThe advance of new technologies in biomedical research has led to a dramatic growth in experimental throughput. Projects therefore steadily grow in size and involve a larger number of researchers. Spreadsheets traditionally used are thus no longer suitable for keeping track of the vast amounts of samples created and need to be replaced with state-of-the-art laboratory information management systems. Such systems have been developed in large numbers, but they are often limited to specific research domains and types of data. One domain so far neglected is the management of libraries of vector clones and genetically engineered cell lines. OpenLabFramework is a newly developed web-application for sample tracking, particularly laid out to fill this gap, but with an open architecture allowing it to be extended for other biological materials and functional data. Its sample tracking mechanism is fully customizable and aids productivity further through support for mobile devices and barcoded labels.\n\nIntroduction \nWith the development of high-throughput technologies, laboratory work has seen a paradigm shift from small projects involving single or few researchers towards large-scale projects involving several laboratories and often hundreds or thousands of samples. Sample management is therefore a growing issue, especially since most laboratories still attempt to keep track of their samples using spreadsheet tools. A high turn-over of academic staff coupled with maintenance of individual files that are often locked or outdated, as well as inconsistent nomenclature and labeling, can lead to tedious repetition of previously existing work. The significant amount of time that is often spent on locating samples would be better used for performing experiments. Moreover, expensive storage space is wasted, since samples are often not labeled properly and cannot be identified. Even if a label is given, it usually does not include a standardized minimal amount of information that allows unambiguous identification of the materials or the experiments they were derived from. Numerous commercial and open-source solutions have been developed in an attempt to overcome these problems.\nAlthough solutions are offered by commercial companies like LabVantage, most academic laboratories find it difficult to afford the license costs, which usually rise with additional users and technical features. The focus of this paper is thus open-source systems.\nAs Table 1 shows, open-source laboratory information management systems (LIMS) are often customized towards specific types of biomaterials or research data, as for instance genotyping[1][2][3], protein production[4][5], protein-protein-interaction[6], 2D gel electrophoresis[7], or protein crystallography[8] data. Some generic LIMS target specific laboratory tasks, such as sample management[3][9][10], laboratory work-flows and protocols[2][11][12][13], documentation, management of lab stocks, or clinical studies.[14] Further solutions exist for molecular genetics and the creation of vector libraries.[15] There is, however, no dedicated LIMS for the management of large vector construct and cell line libraries. At our Lundbeck Foundation Center of Excellence in Nanomedicine (NanoCAN) at the University of Southern Denmark in Odense such large-scale libraries need to be handled efficiently (see Mollenhauer et al.[16] for a short overview about our work). This motivated us to develop a novel open-source LIMS platform: OpenLabFramework (OLF).\n\n\n\n\n\n\n\nTable 1. Some examples of existing browser-based LIMS solutions. Corresponding project URLs can be found in Supplemental Table 1.\n\n\nProject name\n\nRef.\n\nMain purpose\n\nBuilt with\n\n\nMMP-LIMS\n\n[1]\n\nGenome mapping in maize\n\nJava\n\n\nAGL-LIMS\n\n[2]\n\nGenotyping work-flow\n\nJava\n\n\nSMS\n\n[3]\n\nGene mutation screening & biobanking\n\nJava\n\n\nPiMS\n\n[4]\n\nSample & experiment tracking for protein production\n\nJava\n\n\nProteinTracker\n\n[5]\n\nProtein production & purification\n\nJava\n\n\nPARPs Database\n\n[6]\n\nProtein-protein interaction data and data-mining\n\nPerl\/Java\n\n\nLIPAGE\n\n[7]\n\n2D gel electrophoresis based proteomics\n\nPHP\n\n\nLISA\n\n[8]\n\nProtein crystallography\n\nPHP\n\n\nEnzymeTracker\n\n[9]\n\nData analysis, sample management, spreadsheet functionality\n\nPHP\n\n\nFreeLIMS\n\n\n\nSample management, reports\n\nJava\n\n\nYourLabData\n\n\n\nSample tracking and lab notebook\n\n-\n\n\nOpen-LIMS\n\n\n\nExperimental work-flow, sample & document management\n\nPHP\n\n\nOpenFreezer\n\n[10]\n\nSample management & tracking\n\nPHP\/Python\n\n\niLAP\n\n[11]\n\nData management, analysis, experimental protocol design\n\nJava\n\n\nSIGLa\n\n[12]\n\nCustomized experimental work-flows\n\nJava\n\n\nBika\n\n\n\nWhole lab work-flow for clinical studies\n\nPython\n\n\nMicroGen\n\n[13]\n\nMircoarray information and work-flow\n\nMS-Access\n\n\nLabLog\n\n\n\nProject documentation\n\nJava\n\n\nLabStoRe\n\n\n\nChemical lab stocks\n\nPHP\n\n\nSIMBioMS\n\n[14]\n\nLinking experimental, patient, and high-throughput data\n\nPHP\n\n\nMolabIS\n\n[15]\n\nMolecular genetics data\n\nPerl\n\n\n\nResults \nAny LIMS that involves sample management on a large scale should fulfill a number of requirements listed in the following as R1-15. Existing open-source LIMS fulfill these requirements to varying degrees (Table 2).\n\n\n\n\n\n\n\nTable 2. Feature Comparison of requirements across browser-based LIMS solutions for sample management using the following abbreviations: EnzymeTracker (ET), Free-LIMS (FL), SLIMS (SL), YourLabData (YL), Open-LIMS (OL), ProteinTracker (PT), AGL-LIMS (AL), SMS (SM), MolabIS (MI), SIMBioMS (SI), OpenFreezer (OF), and PiMS (PS). \"O\" depicts limited fulfilment. Sample Tracking refers to the physical location of samples. Local Deployment refers to a local installation not requiring a database installation. Cloud Deployment refers to documented cases.\n\n\nRequirements\n\n\n\nET\n\nFL\n\nSL\n\nYL\n\nOL\n\nPT\n\nAL\n\nSM\n\nMI\n\nSI\n\nOF\n\nPS\n\nOLF\n\n\nOpen-source\n\nR1\n\nY\n\nY\n\nY\n\nN\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\n\nModularity\n\nR2\n\nN\n\nN\n\nN\n\nN\n\nY\n\nN\n\nY\n\nN\n\nY\n\nY\n\nY\n\nN\n\nY\n\n\nSample management\n\nR3\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\n\nSample tracking\n\nR4\n\nN\n\nN\n\nO\n\nY\n\nN\n\nN\n\nN\n\nY\n\nY\n\nN\n\nY\n\nY\n\nY\n\n\nFile management\n\nR5\n\nN\n\nN\n\nN\n\nY\n\nY\n\nN\n\nY\n\nN\n\nN\n\nY\n\nN\n\nN\n\nY\n\n\nReports\n\nR6\n\nY\n\nY\n\nY\n\nN\n\nN\n\nY\n\nY\n\nY\n\nY\n\nN\n\nN\n\nN\n\nY\n\n\nMultiple DBMS\n\nR7\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nY\n\nN\n\nN\n\nY\n\nN\n\nY\n\nY\n\n\nLocal deployment\n\nR8\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nY\n\nY\n\nN\n\nN\n\nY\n\n\nCloud deployment\n\nR9\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nY\n\n\nDocumentation\n\nR10\n\nY\n\nN\n\nY\n\nO\n\nY\n\nY\n\nN\n\nY\n\nY\n\nY\n\nY\n\nY\n\nY\n\n\nBarcodes\n\nR11\n\nY\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nY\n\nN\n\nN\n\nN\n\nN\n\nY\n\n\nLabels\n\nR12\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nY\n\nN\n\nN\n\nN\n\nN\n\nY\n\n\nMobile devices\n\nR13\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nY\n\n\nData analysis\n\nR14\n\nY\n\nN\n\nN\n\nN\n\nO\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\nN\n\n\nAudit-logging\n\nR15\n\nY\n\nN\n\nY\n\nN\n\nN\n\nN\n\nN\n\nO\n\nN\n\nN\n\nN\n\nN\n\nN\n\n\n\nImplementation \nA LIMS for an academic environment needs to be open-source (R1), in order to save costs and to allow for adaptation to the specific requirements of a given scientific field and laboratory. Since adaptation can be a difficult and time-consuming task, a LIMS that is modular and extensible by design (R2) would be most appropriate. Although difficult to assess for existing projects, a LIMS should be reliable and its implementation simple. Existing frameworks and software packages that are maintained and tested by a large community are often more reliable than individual solutions and should thus be incorporated.\n\nData handling \nDealing with a large number of samples in a library or biobank requires efficient mechanisms for sample management (R3) and physical sample tracking over several hierarchical levels (R4). Since related information and experimental results are usually stored in additional documents, a management system, where files can be linked to an arbitrary number of samples (R5), would be most useful. Another requirement is that raw data previously entered into the system can be exported to various file formats. This requirement is usually met through an integrated reporting mechanism (R6).\n\nFlexibility in deployment \nAcademic laboratories are often part of an existing IT infrastructure, but support is in many cases limited, e.g. to a single database management system (DBMS), such as MySQL. LIMS deployment should thus be as flexible as possible not be bound to a specific operating system or DBMS. While the first requirement is fulfilled by all LIMS considered in this paper, multiple database support remains an issue (R7). Furthermore, if a suitable server is not available, deployment locally (R8) or to a cloud service (R9) is advantageous.\n\nUser acceptance and excess value \nTriplet et al. have identified approachability as a major hurdle in the acceptance of a LIMS.[9] Modern web-technologies like Ajax allow for a more responsive and intuitive user interface, which in turn improves the user experience and reduces the learning period. Another crucial requirement for a successful adaptation of a LIMS is good documentation (R10). User acceptance can also be improved by offering an excess value over traditional spreadsheet tools, for instance by incorporating the use of barcodes (R11), label printing (R12), and mobile devices, such as smartphones (R13). A further advantage would be the incorporation of data analysis tools directly within the LIMS (R14).\n\nSecurity \nLIMS typically address security concerns by restricting access through secure user logins and different user roles. Security would also be enhanced by audit logging features (R15), where a version number is added to each database entry. Any change will then result in a copy of the entry with a new version number, so that accidentally overwritten entries can be restored.\n\nOpenLabFramework \nWe present OpenLabFramework (OLF), a laboratory information management system (LIMS) primarily targeted at advanced sample and storage management in mid-sized laboratories with less than 50 users. It facilitates a seamless integration of virtual and real world storage handling by making use of mobile devices, which are carried by lab personal anyways, in combination with cheap and fully integrated barcode labeling technology. In the following we shed a light on how OLF fulfills the LIMS requirements that we have identified before (R1\u2013R15). A brief comparison with existing open-source LIMS is given in Table 2.\n\nModularity and extendibility \nOLF is published as open-source (R1) and, due to its modular structure, it can be adapted to different types of laboratory data and sample types. New functionality can also be added and integrated (R2). Various features are covered by the following modules.\nGeneTracker: GeneTracker is intended to fulfill requirements specific to the hierarchical organization of genes, gene variants, vector constructs, and genetically engineered cell lines, thus helping to keep track of extensive sample libraries in the field of targeted genomics. The organization of these samples is further supported through OLF's built-in user and project management features.\nSample storage: The Storage module adds options for tracking and organizing samples in a customizable storage infrastructure (R3\u20134). This infrastructure is hierarchical, starting from buildings and rooms and ending in individual freezers and storage boxes. Interactive grids help the user to assess the content of a storage box at a glance. Together with GeneTracker, samples can be added or removed from storage in an intuitive manner, while providing an overview of remaining copies and related samples.\nFile uploads: The FileAttachments module allows users to up- and download arbitrary files, allowing for a better organization of their results and documents. Files are stored with a combination of timestamp and original file name to avoid conflicts arising from identical file names. Files are uploaded to a configurable folder on the server and not to the database itself. They can be linked to an arbitrary number of samples, so that other users can quickly obtain an overview of files relevant to a sample (R5).\nBarcode and label support: The functionality of the Storage module is complemented by the Barcode module, with which a user can create and print barcode labels (R11\u201312). These can later be used to locate a sample in OLF by scanning the barcode using a USB-connected scanner or a mobile device (R13). The Barcode module currently requires a connected DYMO label printer but can be extended in the future to support other devices.\n\nReporting \nApache POI is utilized to export lists of samples to various file formats, including Excel (XLSX), Open Document Spreadsheets (ODS), PDF, and comma separated values (CSV). This feature is currently available for lists of genes, vector constructs, and cell lines. The storage hierarchy and individual boxes can also be exported to Excel spreadsheets (R6).\n\nFlexibility \nGrails applications are not bound to a specific database management system and will even work with non-SQL solutions, such as MongoDB (R7). OLF is compiled either as WAR file, which is suitable for deployment on a large number of Java-based web containers, or as locally executable JAR file, which comes packed with its own web container and file-based SQL solution (R8). It should be noted that OLF has only been tested thoroughly on Tomcat versions 6 and 7.\n\nCloud deployment \nGrails also offers a plug-in for cloud deployment using the VMware Cloud-Foundry service (http:\/\/www.cloudfoundry.com\/) (R9). Apart from CloudFoundry credentials and memory settings, no further configuration is needed. Upon deployment CloudFoundry automatically configures a suitable database to work with the application.\n\nMobile support \nOLF utilizes the Spring Mobile Grails plug-in to distinguish mobile clients from desktop clients. If a mobile device is detected, a different view is shown that is tailored for the small-sized screen and touch-screen interaction (R13).\n\nUser approachability and excess value \nOLF offers a modern web-interface that is clearly organized and intuitive (Figure 1), and allows for responsive user interaction. The Compass-powered search engine allows users to locate required information quickly and conveniently. Users can also develop effective laboratory work-flows using the sample tracking feature together with barcode labels and mobile devices (Figure 2). OLF validates all user entered data for validity and will, where applicable, provide a list of viable options in form of select boxes. In this way, OLF effectively avoids ambiguity and ensures consistency of sample data. Finally, OLF comes with online documentation that introduces the system to users, administrators, and software developers (R10).\n\n\n\n\n\n\n\n\n\n Figure 1. The web-interface of OLF is divided into four main parts. (A) The header contains a menu and a search field for navigation. (B) A hierarchical project tree found in the left column can also be used for navigation. (C) The main panel is used to render the actual page. It can be further divided into a central panel (1), where properties can be altered, an object history box (2), an operations box with additional links (3), and at the bottom a set of tabs (4) where related information is available and can be interacted with. (D) Additional interaction possibilities are provided through add-ins that can be customized by each user in the right column.\n\n\n\n\n\n\n\n\n\n\n\n\n Figure 2. Initially, the administrators set up master data, such as vectors, cell-lines, medium compositions, as well as the storage infrastructure (*) Users then create projects and link genes to them. Vector clones are created from the genes, which in turn can be used to create cell-line recombinants. Samples are labeled using a DYMO label printer and added to physical, as well as virtual storage. At a later point, the barcode can be used for efficient retrieval and updating of sample information. Moreover, new gene variants and passages can be added with respective new labels and storage locations conveniently. Files and documents can be added to samples and genes, in order to make experimental results and additional information such as related publications, available to other users.\n\n\n\nExample for practical implementation and user acceptance - OLF at the NanoCAN Center \nWithin the past three years since the introduction of the first version of OLF in 2010 at the Lundbeckfonden Center of Excellence NanoCAN, around 780 genes, 1,200 vector constructs, and 300 cell lines have been added to the system, along with 1,500 associated sample locations. Data are stored on a Microsoft SQL Server 2008 installation with a database size of approximately 7\u2005MB. The more than 20 scientists engaged in functional genomics projects were introduced to the system through a one hour feature presentation, which enabled them to use OLF productively. The system was reported to be intuitive, albeit only one user had previous experience in using a LIMS system. Missing functionality considered useful for increased productivity and user convenience, such as handling of barcoded labels, were added to the system subsequently.\n\nRecommended system configuration \nOLF relies on a database backend for storing sample related data. However, only primitive data types, such as numbers or text fields, are persisted to the database itself, while all documents and files are stored in a folder and merely linked in the database. In this way, we expect a database size of less than 10\u201320\u2005MB for most use cases. For smaller laboratories with less than 20 members, the file-based SQL database that is part of OLF's standalone version is appropriate. Since no significant processing of data is required, OLF is expected to be responsive even on systems with a single CPU core. For larger laboratories, however, we recommend using a system with multiple CPU cores and a dedicated database management system, such as MySQL for efficiently dealing with concurrent access in a responsive manner. Due to its dynamic nature, OLF has a large memory footprint and we strongly recommend providing a minimum of 768\u2005MB of RAM on Linux and 1024\u2005MB on Windows.\n\nMethods \nGrails web-application framework \nWe considered the Java based framework Grails to be the most promising candidate for a building a web-application. Grails is a VMWare\/SpringSource product and builds on the company's experience in industry-standard frameworks such as Hibernate or Spring, which also form the core of Grails. In Grails, plug-ins deliver high-quality solutions for non-trivial web application tasks, e.g. database search (Compass and Apache Lucene), spreadsheet im- and export (Apache POI) and a user\/security management (SpringSecurity). Grails embraces the paradigms convention over configuration and separation of concerns to keep the code concise and clean. Furthermore, Grails hides the complexity of data persistence with an object relational modeling technique, which encapsulates all database interactions and models them through Java domain classes. These characteristics allow faster development and integration of new features.\n\nOpenLabFramework \nAs illustrated in Figure 3, OLF has a modular structure, in which a back-end plug-in provides the necessary base classes, as well as user, project and security management. Content plug-ins can then add arbitrary classes and view templates, and integrate with other plug-ins. All plug-ins are finally merged in the front-end application, which utilizes the scaffolding mechanism of Grails to dynamically create Ajax-driven views for user interaction.\n\n\n\n\n\n\n\n\n\n Figure 3. OpenLabFramework is built in a strictly modular fashion. A back-end module provides the basic functionality, including project and user management, as well as base classes for other modules. Additional modules extend the base classes and integrate with existing ones. Finally, the front-end module creates views for all defined content and allows for interaction through a responsive web-interface.\n\n\n\nThe back-end of OLF introduces two base classes called MasterDataObject and DataObject (Figure 4). MasterDataObjects can be extended by classes representing master data that are maintained by system administrators, e.g. wildtype cell lines or vector systems in the GeneTracker module, or freezers and storage locations in the Storage module. More dynamic content is expressed through DataObject classes, which can be created and modified by regular users, e.g. genes or genetically engineered cell lines in the GeneTracker module, or StorageElements, which contain location data for other DataObject instances, in the StorageModule. This hierarchy makes OLF highly generic, but also allows fine-grained interactions between more specialized classes.\n\r\n\n\n\n\n\n\n\n\n\n\n Figure 4. The back-end provides two classes MasterDataObject (MDO) and DataObject (DO) that are extended by the different modules. MDOs can only be created by administrators, whereas DOs can be created by any user. Existing DOs and MDOs can be combined freely by module developers in order to build complex hierarchies.\n\n\n\nOLF strictly follows established patterns found in software architecture. Code is separated into different functional layers according to the model-view-controller pattern. In addition, business logic related code is bundled in service classes and tag libraries to avoid code duplication. Furthermore, OLF introduces the concept of content modules, which can be attached to existing pages. Content modules can either contribute new links to OLF's menu, render additional add-ins or tabs, or provide additional links called operations (Figure 1). By providing a clear structure and suitable interfaces, other developers can thus easily contribute to OLF.\n\nDiscussion \nNumerous commercial and open-source laboratory information management systems (LIMS) exist today. However, since commercial licenses are expensive and lack the possibility to be adapted to specific needs without additional costs, academic laboratories usually focus on finding an open-source solution to their sample management issues. Moreover, none of the existing solutions seems optimal for all given tasks (Table 2). Naturally, most LIMS are dedicated to a specific field of research and are thus not generally suited for other fields. Some solutions, on the other hand, focus on certain general aspects of laboratory work, such as sample tracking, protocols, or work-flows.\nOpenLabFramework (OLF) was developed to address the need for an open-source LIMS solution for covering vector constructs and cell line library sample tracking. Acknowledging that many LIMS remain limited to their research domain, we created OLF in a strictly modular and extensible fashion, with dedicated modules for sample tracking, barcoded label printing, and file management. We expect that OLF can be adapted to other research fields and biomaterials with minimal developmental effort by implementing a content module similar to GeneTracker, which is then complemented by plugging in additional features as needed.\nWe built OLF using Grails and its extensive plug-in eco-system. This allows OLF to satisfy basic software development requirements, such as flexibility, reliability and simplicity. The use of a solid framework allows developers to focus on user-specific requirements, as for instance the support for mobile devices, and to keep the application up-to-date, since it will improve together with the underlying framework. The use of Grails, which can be considered the most dynamic and flexible web-application framework available in Java, together with its plug-ins, poses a significant simplification when adding new web-application features. This advantage separates OLF from comparable LIMS, which also embrace the concept of modularity or the use of web-application frameworks.\nThe introduction of OLF allows controlling sample logistics effectively, which is a particular challenge upon movement, turn-over of lab staff, and improper labeling of samples. OLF may further increase productivity by including modern technologies so far disregarded by most other open-source LIMS, such as printing and reading barcode labels. The high degree of automation and standardization that can be achieved by this may substantially reduce user-caused errors in sample assignment. A web-layer for mobile devices provides an additional advantage. In this way, samples can now be removed from physical and virtual storage at the same time, thus limiting the risk of forgetting this step after the work with the sample is completed. As illustrated in Figure 2, the implementation of OLF in a laboratory environment can lead to a significantly more productive work-flow.\nFinally, unlike most LIMS, OLF is not bound to a specific database or web-container. OLF can be coupled with a large number of database management systems, including non-SQL solutions like MongoDB. If a suitable server is not available, OLF can be installed locally or even be deployed to the cloud with little effort, as demonstrated in our demo application. This flexibility will reduce technical hurdles in the introduction of OLF to a new laboratory.\nOLF offers efficient and user-friendly management of sample information and location in the field of high-throughput biology and functional genomics. Being extensible, it can be adapted to satisfy additional requirements with little developmental effort. One requirement currently neglected is the extensive integration of additional web tools, which would make OLF more attractive to end-users. Although result data files can be uploaded and linked to samples, we envision that direct interfacing with laboratory equipment would make result data management significantly more convenient. The implementation of RESTful web services could expose OLF data sets and functionality to other tools and information systems. Along with this, the reporting capabilities could be improved, allowing for customized reports, where information from several instances is pooled. This would also help in establishing data analysis directly within OLF or through integration of additional tools (R15). Another important aspect worth considering is that OLF might in some instances require a more fine-grained access to the data. This functionality could be added through additional user roles or access control lists. Finally, the creation of a dedicated app for mobile platforms, such as Android or iOS, would improve the mobile user experience.\n\nConclusions \nIn order to retain an overview over large sample libraries typically found in nowadays laboratories, an efficient system for management and tracking of samples is required. OpenLabFramework (OLF) has been developed with focus on vector construct and cell line libraries. Thanks to its modularity, however, it can be adapted to new scenarios. OLF can be deployed using different database management systems either locally, to a server, or to the cloud. The incorporation of modern technologies, such as mobile devices and printing of barcode labels may increase productivity even further. These properties together may be considered characteristic for a next-generation LIMS and should provide the potential for widespread adaptation.\nOLF embraces open-source in the hope of attracting not only laboratories in need of a LIMS, but also a community of software developers willing to adapt OLF to new scenarios. We intend to contribute in the future by developing further modules, e.g. for seamless evaluation of experimental data by integration of third party tools. Consequent utilization of community-proven open-source libraries make OLF's backend already highly reliable. With the support of its own community, OLF as a whole is expected to reach the same high quality standard in the future.\n\nAdditional information \nAvailability and Requirements \nProject name: OpenLabFramework\nURL: https:\/\/github.com\/NanoCAN\/OpenLabFramework\nWiki: https:\/\/github.com\/NanoCAN\/OpenLabFramework\/wiki\nDemo: http:\/\/www.nanocan.dk\/openlabframework\/demo (user: admin, password: demo0815)\nOperating system(s): Platform independent\nProgramming language: Java, Groovy, Java-script\nOther requirements: Java 1.6 or higher, Tomcat 6.0 or higher\nLicense: GNU GPL v3\n\nAcknowledgements \nThis work was supported by the Lundbeckfonden grant for the NanoCAN Center of Excellence in Nanomedicine, the Region Syddanmarks ph.d.-pulje and Forskningspulje, the Fonden Til L\u00e6gevidenskabens Fremme, and co-financed by the INTERREG 4 A-program Syddanmark-Schleswig-K.E.R.N. with funds from The European Regional Development Fund.\n\nAuthor information \nAffiliations \nLundbeckfonden Center of Excellence in Nanomedicine NanoCAN, University of Southern Denmark, Odense, DK\nMarkus List, Steffen Schmidt, Jakub Trojnar, Mads Thomassen, Torben A. Kruse & Jan Mollenhauer\nInstitute of Molecular Medicin (IMM), University of Southern Denmark, Odense, DK\nMarkus List, Steffen Schmidt, Jakub Trojnar & Jan Mollenhauer\nClinical Institute (CI), University of Southern Denmark, Odense, DK\nMarkus List, Mads Thomassen, Torben A. Kruse & Qihua Tan\nEpidemiology, Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark, Odense, DK\nQihua Tan\nDepartment of Biochemistry and Molecular Biology (BMB), University of Southern Denmark, Odense, DK\nJakub Trojnar\nio-consultants GmbH & Co. KG, Heidelberg, DE\nJochen Thomas\nDepartment of Mathematics and Computer Science (IMADA), University of Southern Denmark, Odense, DK\nJan Baumbach\n\nContributions \nM.L. and J.Th. developed the software requirement specification. S.S. and J.Tr. specified requirements specific to the biomedical domain and contributed extensively to bug-tracking and regular testing of OLF. ML implemented the application. M.T., T.K., Q.T., J.B. and J.M. jointly supervised the project, designed graphics and work-flow diagrams. All authors contributed equally to drafting the manuscript. All authors read and approved the final manuscript.\n\nCompeting interests \nThe authors declare no competing financial interests.\n\nCorresponding author \nCorrespondence to Markus List.\n\nSupplementary information \nPDF files\n1.Supplementary Information: OpenLabFramework Supplemental Material\n\nReferences \n\n\n\u2191 1.0 1.1 Sanchez-Villeda, H.; Schroeder, S.; Polacco, M. et al. (2003). \"Development of an integrated laboratory information management system for the maize mapping project\". Bioinformatics 19 (16): 2022-2030. doi:10.1093\/bioinformatics\/btg274. PMID 14594706.   \n\n\u2191 2.0 2.1 2.2 Jayashree, B.; Reddy, P.T.; Leeladevi, Y. et al. (2006). \"Laboratory information management software for genotyping workflows: Applications in high throughput crop genotyping\". 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PMC PMC3436699. PMID 22574679. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3436699 .   \n\n\u2191 6.0 6.1 Droit, A.; Hunter, J.M.; Rouleau, M. et al. (2007). \"PARPs database: A LIMS systems for protein-protein interaction data mining or laboratory information management system\". BMC Bioinformatics 8: 483. doi:10.1186\/1471-2105-8-483. PMC PMC2266781. PMID 18093328. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2266781 .   \n\n\u2191 7.0 7.1 Morisawa, H.; Hirota, M.; Toda, T. (2006). \"Development of an open source laboratory information management system for 2-D gel electrophoresis-based proteomics workflow\". BMC Bioinformatics 7: 430. doi:10.1186\/1471-2105-7-430. PMC PMC1599757. PMID 17018156. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1599757 .   \n\n\u2191 8.0 8.1 Haebel, P.W.; Arcus, V.L.; Baker, E.N.; Metcalf, P. (2001). \"LISA: An intranet-based flexible database for protein crystallography project management\". Acta Crystallographica Section D 57 (Pt 9): 1341-1343. doi:10.1107\/S0907444901009295. PMID 11526339.   \n\n\u2191 9.0 9.1 9.2 Triplet, T.; Butler, G. (2012). \"The EnzymeTracker: An open-source laboratory information management system for sample tracking\". BMC Bioinformatics 13 (15): 1341-1343. doi:10.1186\/1471-2105-13-15. PMC PMC3353834. PMID 22280360. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3353834 .   \n\n\u2191 10.0 10.1 Olhovsky, M.; Williton, K.; Dai, A.Y. et al. (2011). \"OpenFreezer: A reagent information management software system\". Nature Methods 8 (8): 612\u2013613. doi:10.1038\/nmeth.1658. PMID 21799493.   \n\n\u2191 11.0 11.1 Stocker, G.; Fischer, M.; Rieder, D. et al. (2009). \"iLAP: a workflow-driven software for experimental protocol development, data acquisition and analysis\". BMC Bioinformatics 10: 390. doi:10.1186\/1471-2105-10-390. PMC PMC2789074. PMID 19941647. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2789074 .   \n\n\u2191 12.0 12.1 Melo, Alexandre; Alessandra Faria-Campos; Daiane M DeLaat; Rodrigo Keller; Vin\u00edcius Abreu; S\u00e9rgio Campos (2010). \"SIGLa: an adaptable LIMS for multiple laboratories\". BMC Genomics 11 (Suppl 5): S8. doi:10.1186\/1471-2164-11-S5-S8. PMC PMC3045801. PMID 21210974. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3045801 .   \n\n\u2191 13.0 13.1 Burgarella, S.; Cattaneo, D.; Pinciroli, F.; Masseroli, M. (2005). \"MicroGen: a MIAME compliant web system for microarray experiment information and workflow management\". BMC Bioinformatics 6 (Suppl 4): S6. doi:10.1186\/1471-2105-6-S4-S6. PMC PMC1866379. PMID 16351755. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1866379 .   \n\n\u2191 14.0 14.1 Krestyaninova, M.; Zarins, A.; Viksna, J. et al. (2009). \"A system for information management in biomedical studies \u2013 SIMBioMS\". Bioinformatics 25 (20): 2768-2769. doi:10.1093\/bioinformatics\/btp420. PMC PMC2759553. PMID 19633095. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2759553 .   \n\n\u2191 15.0 15.1 Truong, C.V.C.; Groeneveld, L.F.; Morgenstern, B.; Groeneveld, E. (2011). \"MolabIS - An integrated information system for storing and managing molecular genetics data\". BMC Bioinformatics 12: 425. doi:10.1186\/1471-2105-12-425. PMC PMC3268772. PMID 22040322. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3268772 .   \n\n\u2191 Mollenhauer, J.; Stamou, D.; Flyvbjerg, A. et al. (2010). \"David versus Goliath\". Nanomedicine 6 (4): 504\u2013509. doi:10.1016\/j.nano.2010.04.002. PMID 20417315.   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. In Table 2, checkmarks and Xs were replaced with Ys and Ns. The \"Methods\" section has also been moved from the end to a more logical position before the Discussion and Conclusion.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Efficient_sample_tracking_with_OpenLabFramework\">https:\/\/www.limswiki.org\/index.php\/Journal:Efficient_sample_tracking_with_OpenLabFramework<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on bioinformaticsLIMSwiki journal articles on software\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 25 January 2016, at 20:04.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 1,631 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","241f9c1d4812074890e77322c80e615c_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_Efficient_sample_tracking_with_OpenLabFramework skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Efficient sample tracking with OpenLabFramework<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>The advance of new technologies in biomedical research has led to a dramatic growth in experimental throughput. Projects therefore steadily grow in size and involve a larger number of researchers. Spreadsheets traditionally used are thus no longer suitable for keeping track of the vast amounts of samples created and need to be replaced with state-of-the-art <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" target=\"_blank\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">laboratory information management systems<\/a>. Such systems have been developed in large numbers, but they are often limited to specific research domains and types of data. One domain so far neglected is the management of libraries of vector clones and genetically engineered cell lines. <a href=\"https:\/\/www.limswiki.org\/index.php\/OpenLabFramework\" title=\"OpenLabFramework\" target=\"_blank\" class=\"wiki-link\" data-key=\"c1144498854bca66b3ac289f2e0bc51b\">OpenLabFramework<\/a> is a newly developed web-application for sample tracking, particularly laid out to fill this gap, but with an open architecture allowing it to be extended for other biological materials and functional data. Its sample tracking mechanism is fully customizable and aids productivity further through support for mobile devices and barcoded labels.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>With the development of high-throughput technologies, <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" target=\"_blank\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratory<\/a> work has seen a paradigm shift from small projects involving single or few researchers towards large-scale projects involving several laboratories and often hundreds or thousands of samples. Sample management is therefore a growing issue, especially since most laboratories still attempt to keep track of their samples using spreadsheet tools. A high turn-over of academic staff coupled with maintenance of individual files that are often locked or outdated, as well as inconsistent nomenclature and labeling, can lead to tedious repetition of previously existing work. The significant amount of time that is often spent on locating samples would be better used for performing experiments. Moreover, expensive storage space is wasted, since samples are often not labeled properly and cannot be identified. Even if a label is given, it usually does not include a standardized minimal amount of information that allows unambiguous identification of the materials or the experiments they were derived from. Numerous commercial and open-source solutions have been developed in an attempt to overcome these problems.\n<\/p><p>Although solutions are offered by commercial companies like <a href=\"https:\/\/www.limswiki.org\/index.php\/LabVantage_Solutions,_Inc.\" title=\"LabVantage Solutions, Inc.\" target=\"_blank\" class=\"wiki-link\" data-key=\"1855d5158d4dd8f748e925e626daf5ee\">LabVantage<\/a>, most academic laboratories find it difficult to afford the license costs, which usually rise with additional users and technical features. The focus of this paper is thus open-source systems.\n<\/p><p>As Table 1 shows, <a href=\"https:\/\/www.limswiki.org\/index.php\/Category:Laboratory_information_management_systems_(open_source)\" title=\"Category:Laboratory information management systems (open source)\" target=\"_blank\" class=\"wiki-link\" data-key=\"3ddf885cb75e1140d0fc0cc2480d3895\">open-source laboratory information management systems<\/a> (LIMS) are often customized towards specific types of biomaterials or research data, as for instance genotyping<sup id=\"rdp-ebb-cite_ref-Sanchez-VilledaDev03_1-0\" class=\"reference\"><a href=\"#cite_note-Sanchez-VilledaDev03-1\" rel=\"external_link\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-JayashreeLab06_2-0\" class=\"reference\"><a href=\"#cite_note-JayashreeLab06-2\" rel=\"external_link\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-VoegeleASamp10_3-0\" class=\"reference\"><a href=\"#cite_note-VoegeleASamp10-3\" rel=\"external_link\">[3]<\/a><\/sup>, protein production<sup id=\"rdp-ebb-cite_ref-MorrisThePro11_4-0\" class=\"reference\"><a href=\"#cite_note-MorrisThePro11-4\" rel=\"external_link\">[4]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-PonkoPro12_5-0\" class=\"reference\"><a href=\"#cite_note-PonkoPro12-5\" rel=\"external_link\">[5]<\/a><\/sup>, protein-protein-interaction<sup id=\"rdp-ebb-cite_ref-DroitPARPS07_6-0\" class=\"reference\"><a href=\"#cite_note-DroitPARPS07-6\" rel=\"external_link\">[6]<\/a><\/sup>, 2D gel electrophoresis<sup id=\"rdp-ebb-cite_ref-MorisawaDev06_7-0\" class=\"reference\"><a href=\"#cite_note-MorisawaDev06-7\" rel=\"external_link\">[7]<\/a><\/sup>, or protein crystallography<sup id=\"rdp-ebb-cite_ref-HaebelLISA01_8-0\" class=\"reference\"><a href=\"#cite_note-HaebelLISA01-8\" rel=\"external_link\">[8]<\/a><\/sup> data. Some generic LIMS target specific laboratory tasks, such as sample management<sup id=\"rdp-ebb-cite_ref-VoegeleASamp10_3-1\" class=\"reference\"><a href=\"#cite_note-VoegeleASamp10-3\" rel=\"external_link\">[3]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-TripletTheEnz12_9-0\" class=\"reference\"><a href=\"#cite_note-TripletTheEnz12-9\" rel=\"external_link\">[9]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-OlhovskyOpen11_10-0\" class=\"reference\"><a href=\"#cite_note-OlhovskyOpen11-10\" rel=\"external_link\">[10]<\/a><\/sup>, laboratory work-flows and protocols<sup id=\"rdp-ebb-cite_ref-JayashreeLab06_2-1\" class=\"reference\"><a href=\"#cite_note-JayashreeLab06-2\" rel=\"external_link\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-Stocker_iLAP09_11-0\" class=\"reference\"><a href=\"#cite_note-Stocker_iLAP09-11\" rel=\"external_link\">[11]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-MeloSIGLa10_12-0\" class=\"reference\"><a href=\"#cite_note-MeloSIGLa10-12\" rel=\"external_link\">[12]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-BurgarellaMicro05_13-0\" class=\"reference\"><a href=\"#cite_note-BurgarellaMicro05-13\" rel=\"external_link\">[13]<\/a><\/sup>, documentation, management of lab stocks, or clinical studies.<sup id=\"rdp-ebb-cite_ref-KrestyaninovaASys09_14-0\" class=\"reference\"><a href=\"#cite_note-KrestyaninovaASys09-14\" rel=\"external_link\">[14]<\/a><\/sup> Further solutions exist for molecular genetics and the creation of vector libraries.<sup id=\"rdp-ebb-cite_ref-TruongMolab11_15-0\" class=\"reference\"><a href=\"#cite_note-TruongMolab11-15\" rel=\"external_link\">[15]<\/a><\/sup> There is, however, no dedicated LIMS for the management of large vector construct and cell line libraries. At our Lundbeck Foundation Center of Excellence in Nanomedicine (NanoCAN) at the University of Southern Denmark in Odense such large-scale libraries need to be handled efficiently (see Mollenhauer et al.<sup id=\"rdp-ebb-cite_ref-MollenhauerDavid10_16-0\" class=\"reference\"><a href=\"#cite_note-MollenhauerDavid10-16\" rel=\"external_link\">[16]<\/a><\/sup> for a short overview about our work). This motivated us to develop a novel open-source LIMS platform: <a href=\"https:\/\/www.limswiki.org\/index.php\/OpenLabFramework\" title=\"OpenLabFramework\" target=\"_blank\" class=\"wiki-link\" data-key=\"c1144498854bca66b3ac289f2e0bc51b\">OpenLabFramework<\/a> (OLF).\n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" colspan=\"4\"><b>Table 1. Some examples of existing browser-based LIMS solutions.<\/b> Corresponding project URLs can be found in <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/article-assets\/npg\/srep\/2014\/140304\/srep04278\/extref\/srep04278-s1.pdf\" target=\"_blank\">Supplemental Table 1<\/a>.\n<\/td><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">Project name\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Ref.\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Main purpose\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Built with\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">MMP-LIMS\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-Sanchez-VilledaDev03_1-1\" class=\"reference\"><a href=\"#cite_note-Sanchez-VilledaDev03-1\" rel=\"external_link\">[1]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Genome mapping in maize\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Java\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">AGL-LIMS\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-JayashreeLab06_2-2\" class=\"reference\"><a href=\"#cite_note-JayashreeLab06-2\" rel=\"external_link\">[2]<\/a><\/sup>\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Genotyping work-flow\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Java\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">SMS\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-VoegeleASamp10_3-2\" class=\"reference\"><a href=\"#cite_note-VoegeleASamp10-3\" rel=\"external_link\">[3]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Gene mutation screening & biobanking\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Java\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">PiMS\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-MorrisThePro11_4-1\" class=\"reference\"><a href=\"#cite_note-MorrisThePro11-4\" rel=\"external_link\">[4]<\/a><\/sup>\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Sample & experiment tracking for protein production\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Java\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ProteinTracker\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-PonkoPro12_5-1\" class=\"reference\"><a href=\"#cite_note-PonkoPro12-5\" rel=\"external_link\">[5]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Protein production & purification\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Java\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">PARPs Database\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-DroitPARPS07_6-1\" class=\"reference\"><a href=\"#cite_note-DroitPARPS07-6\" rel=\"external_link\">[6]<\/a><\/sup>\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Protein-protein interaction data and data-mining\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Perl\/Java\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LIPAGE\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-MorisawaDev06_7-1\" class=\"reference\"><a href=\"#cite_note-MorisawaDev06-7\" rel=\"external_link\">[7]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2D gel electrophoresis based proteomics\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PHP\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">LISA\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-HaebelLISA01_8-1\" class=\"reference\"><a href=\"#cite_note-HaebelLISA01-8\" rel=\"external_link\">[8]<\/a><\/sup>\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Protein crystallography\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">PHP\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">EnzymeTracker\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-TripletTheEnz12_9-1\" class=\"reference\"><a href=\"#cite_note-TripletTheEnz12-9\" rel=\"external_link\">[9]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Data analysis, sample management, spreadsheet functionality\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PHP\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">FreeLIMS\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Sample management, reports\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Java\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">YourLabData\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Sample tracking and lab notebook\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">Open-LIMS\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Experimental work-flow, sample & document management\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">PHP\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">OpenFreezer\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-OlhovskyOpen11_10-1\" class=\"reference\"><a href=\"#cite_note-OlhovskyOpen11-10\" rel=\"external_link\">[10]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Sample management & tracking\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PHP\/Python\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">iLAP\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-Stocker_iLAP09_11-1\" class=\"reference\"><a href=\"#cite_note-Stocker_iLAP09-11\" rel=\"external_link\">[11]<\/a><\/sup>\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Data management, analysis, experimental protocol design\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Java\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">SIGLa\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-MeloSIGLa10_12-1\" class=\"reference\"><a href=\"#cite_note-MeloSIGLa10-12\" rel=\"external_link\">[12]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Customized experimental work-flows\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Java\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">Bika\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Whole lab work-flow for clinical studies\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Python\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">MicroGen\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-BurgarellaMicro05_13-1\" class=\"reference\"><a href=\"#cite_note-BurgarellaMicro05-13\" rel=\"external_link\">[13]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Mircoarray information and work-flow\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">MS-Access\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">LabLog\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Project documentation\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Java\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LabStoRe\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Chemical lab stocks\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PHP\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">SIMBioMS\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-KrestyaninovaASys09_14-1\" class=\"reference\"><a href=\"#cite_note-KrestyaninovaASys09-14\" rel=\"external_link\">[14]<\/a><\/sup>\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Linking experimental, patient, and high-throughput data\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">PHP\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">MolabIS\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><sup id=\"rdp-ebb-cite_ref-TruongMolab11_15-1\" class=\"reference\"><a href=\"#cite_note-TruongMolab11-15\" rel=\"external_link\">[15]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Molecular genetics data\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Perl\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h2><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h2>\n<p>Any LIMS that involves sample management on a large scale should fulfill a number of requirements listed in the following as R1-15. Existing open-source LIMS fulfill these requirements to varying degrees (Table 2).\n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" colspan=\"15\"><b>Table 2. Feature Comparison of requirements across browser-based LIMS solutions for sample management using the following abbreviations:<\/b> EnzymeTracker (ET), Free-LIMS (FL), SLIMS (SL), YourLabData (YL), Open-LIMS (OL), ProteinTracker (PT), AGL-LIMS (AL), SMS (SM), MolabIS (MI), SIMBioMS (SI), OpenFreezer (OF), and PiMS (PS). \"O\" depicts limited fulfilment. Sample Tracking refers to the physical location of samples. Local Deployment refers to a local installation not requiring a database installation. Cloud Deployment refers to documented cases.\n<\/td><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">Requirements\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">ET\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">FL\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">SL\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">YL\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">OL\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">PT\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">AL\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">SM\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">MI\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">SI\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">OF\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">PS\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">OLF\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Open-source\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">R1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">Modularity\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">R2\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Sample management\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">R3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">Sample tracking\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">R4\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">O\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">File management\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">R5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">Reports\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">R6\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Multiple DBMS\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">R7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">Local deployment\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">R8\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Cloud deployment\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">R9\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">Documentation\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">R10\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">O\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Barcodes\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">R11\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">Labels\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">R12\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Mobile devices\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">R13\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\">Data analysis\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">R14\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">O\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"padding-left:10px; padding-right:10px;\">N\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Audit-logging\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">R15\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">O\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h3><span class=\"mw-headline\" id=\"Implementation\">Implementation<\/span><\/h3>\n<p>A LIMS for an academic environment needs to be open-source (R1), in order to save costs and to allow for adaptation to the specific requirements of a given scientific field and laboratory. Since adaptation can be a difficult and time-consuming task, a LIMS that is modular and extensible by design (R2) would be most appropriate. Although difficult to assess for existing projects, a LIMS should be reliable and its implementation simple. Existing frameworks and software packages that are maintained and tested by a large community are often more reliable than individual solutions and should thus be incorporated.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Data_handling\">Data handling<\/span><\/h3>\n<p>Dealing with a large number of samples in a library or biobank requires efficient mechanisms for sample management (R3) and physical sample tracking over several hierarchical levels (R4). Since related information and experimental results are usually stored in additional documents, a management system, where files can be linked to an arbitrary number of samples (R5), would be most useful. Another requirement is that raw data previously entered into the system can be exported to various file formats. This requirement is usually met through an integrated reporting mechanism (R6).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Flexibility_in_deployment\">Flexibility in deployment<\/span><\/h3>\n<p>Academic laboratories are often part of an existing IT infrastructure, but support is in many cases limited, e.g. to a single database management system (DBMS), such as <a href=\"https:\/\/www.limswiki.org\/index.php\/MySQL\" title=\"MySQL\" target=\"_blank\" class=\"wiki-link\" data-key=\"35005451bfcd508bce47c58e72260128\">MySQL<\/a>. LIMS deployment should thus be as flexible as possible not be bound to a specific operating system or DBMS. While the first requirement is fulfilled by all LIMS considered in this paper, multiple database support remains an issue (R7). Furthermore, if a suitable server is not available, deployment locally (R8) or to a cloud service (R9) is advantageous.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"User_acceptance_and_excess_value\">User acceptance and excess value<\/span><\/h3>\n<p>Triplet et al. have identified approachability as a major hurdle in the acceptance of a LIMS.<sup id=\"rdp-ebb-cite_ref-TripletTheEnz12_9-2\" class=\"reference\"><a href=\"#cite_note-TripletTheEnz12-9\" rel=\"external_link\">[9]<\/a><\/sup> Modern web-technologies like Ajax allow for a more responsive and intuitive user interface, which in turn improves the user experience and reduces the learning period. Another crucial requirement for a successful adaptation of a LIMS is good documentation (R10). User acceptance can also be improved by offering an excess value over traditional spreadsheet tools, for instance by incorporating the use of barcodes (R11), label printing (R12), and mobile devices, such as smartphones (R13). A further advantage would be the incorporation of data analysis tools directly within the LIMS (R14).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Security\">Security<\/span><\/h3>\n<p>LIMS typically address security concerns by restricting access through secure user logins and different user roles. Security would also be enhanced by audit logging features (R15), where a version number is added to each database entry. Any change will then result in a copy of the entry with a new version number, so that accidentally overwritten entries can be restored.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"OpenLabFramework\">OpenLabFramework<\/span><\/h3>\n<p>We present OpenLabFramework (OLF), a laboratory information management system (LIMS) primarily targeted at advanced sample and storage management in mid-sized laboratories with less than 50 users. It facilitates a seamless integration of virtual and real world storage handling by making use of mobile devices, which are carried by lab personal anyways, in combination with cheap and fully integrated barcode labeling technology. In the following we shed a light on how OLF fulfills the LIMS requirements that we have identified before (R1\u2013R15). A brief comparison with existing open-source LIMS is given in Table 2.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Modularity_and_extendibility\">Modularity and extendibility<\/span><\/h4>\n<p>OLF is published as open-source (R1) and, due to its modular structure, it can be adapted to different types of laboratory data and sample types. New functionality can also be added and integrated (R2). Various features are covered by the following modules.\n<\/p><p><i>GeneTracker<\/i>: GeneTracker is intended to fulfill requirements specific to the hierarchical organization of genes, gene variants, vector constructs, and genetically engineered cell lines, thus helping to keep track of extensive sample libraries in the field of targeted genomics. The organization of these samples is further supported through OLF's built-in user and project management features.\n<\/p><p><i>Sample storage<\/i>: The Storage module adds options for tracking and organizing samples in a customizable storage infrastructure (R3\u20134). This infrastructure is hierarchical, starting from buildings and rooms and ending in individual freezers and storage boxes. Interactive grids help the user to assess the content of a storage box at a glance. Together with GeneTracker, samples can be added or removed from storage in an intuitive manner, while providing an overview of remaining copies and related samples.\n<\/p><p><i>File uploads<\/i>: The FileAttachments module allows users to up- and download arbitrary files, allowing for a better organization of their results and documents. Files are stored with a combination of timestamp and original file name to avoid conflicts arising from identical file names. Files are uploaded to a configurable folder on the server and not to the database itself. They can be linked to an arbitrary number of samples, so that other users can quickly obtain an overview of files relevant to a sample (R5).\n<\/p><p><i>Barcode and label support<\/i>: The functionality of the Storage module is complemented by the Barcode module, with which a user can create and print barcode labels (R11\u201312). These can later be used to locate a sample in OLF by scanning the barcode using a USB-connected scanner or a mobile device (R13). The Barcode module currently requires a connected DYMO label printer but can be extended in the future to support other devices.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Reporting\">Reporting<\/span><\/h4>\n<p>Apache POI is utilized to export lists of samples to various file formats, including Excel (XLSX), Open Document Spreadsheets (ODS), PDF, and comma separated values (CSV). This feature is currently available for lists of genes, vector constructs, and cell lines. The storage hierarchy and individual boxes can also be exported to Excel spreadsheets (R6).\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Flexibility\">Flexibility<\/span><\/h4>\n<p>Grails applications are not bound to a specific database management system and will even work with non-SQL solutions, such as MongoDB (R7). OLF is compiled either as WAR file, which is suitable for deployment on a large number of Java-based web containers, or as locally executable JAR file, which comes packed with its own web container and file-based SQL solution (R8). It should be noted that OLF has only been tested thoroughly on <a href=\"https:\/\/www.limswiki.org\/index.php\/Apache_Tomcat\" title=\"Apache Tomcat\" target=\"_blank\" class=\"wiki-link\" data-key=\"6fd6693ebebef576e0e80cf1c328d360\">Tomcat<\/a> versions 6 and 7.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Cloud_deployment\">Cloud deployment<\/span><\/h4>\n<p>Grails also offers a plug-in for cloud deployment using the VMware Cloud-Foundry service (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.cloudfoundry.com\/\" target=\"_blank\">http:\/\/www.cloudfoundry.com\/<\/a>) (R9). Apart from CloudFoundry credentials and memory settings, no further configuration is needed. Upon deployment CloudFoundry automatically configures a suitable database to work with the application.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Mobile_support\">Mobile support<\/span><\/h4>\n<p>OLF utilizes the Spring Mobile Grails plug-in to distinguish mobile clients from desktop clients. If a mobile device is detected, a different view is shown that is tailored for the small-sized screen and touch-screen interaction (R13).\n<\/p>\n<h4><span class=\"mw-headline\" id=\"User_approachability_and_excess_value\">User approachability and excess value<\/span><\/h4>\n<p>OLF offers a modern web-interface that is clearly organized and intuitive (Figure 1), and allows for responsive user interaction. The Compass-powered search engine allows users to locate required information quickly and conveniently. Users can also develop effective laboratory work-flows using the sample tracking feature together with barcode labels and mobile devices (Figure 2). OLF validates all user entered data for validity and will, where applicable, provide a list of viable options in form of select boxes. In this way, OLF effectively avoids ambiguity and ensures consistency of sample data. Finally, OLF comes with online documentation that introduces the system to users, administrators, and software developers (R10).\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_List_ScientificReports2014_4.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"d2af694764e5563d5993b17743b84ca8\"><img alt=\"Fig1 List ScientificReports2014 4.jpg\" src=\"https:\/\/www.limswiki.org\/images\/4\/49\/Fig1_List_ScientificReports2014_4.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 1. The web-interface of OLF is divided into four main parts.<\/b> (A) The header contains a menu and a search field for navigation. (B) A hierarchical project tree found in the left column can also be used for navigation. (C) The main panel is used to render the actual page. It can be further divided into a central panel (1), where properties can be altered, an object history box (2), an operations box with additional links (3), and at the bottom a set of tabs (4) where related information is available and can be interacted with. (D) Additional interaction possibilities are provided through add-ins that can be customized by each user in the right column.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_List_ScientificReports2014_4.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"4fef9a69b260bc000270dc5612a44ff4\"><img alt=\"Fig2 List ScientificReports2014 4.jpg\" src=\"https:\/\/www.limswiki.org\/images\/3\/31\/Fig2_List_ScientificReports2014_4.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 2. Initially, the administrators set up master data, such as vectors, cell-lines, medium compositions, as well as the storage infrastructure (*)<\/b> Users then create projects and link genes to them. Vector clones are created from the genes, which in turn can be used to create cell-line recombinants. Samples are labeled using a DYMO label printer and added to physical, as well as virtual storage. At a later point, the barcode can be used for efficient retrieval and updating of sample information. Moreover, new gene variants and passages can be added with respective new labels and storage locations conveniently. Files and documents can be added to samples and genes, in order to make experimental results and additional information such as related publications, available to other users.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h4><span class=\"mw-headline\" id=\"Example_for_practical_implementation_and_user_acceptance_-_OLF_at_the_NanoCAN_Center\">Example for practical implementation and user acceptance - OLF at the NanoCAN Center<\/span><\/h4>\n<p>Within the past three years since the introduction of the first version of OLF in 2010 at the Lundbeckfonden Center of Excellence NanoCAN, around 780 genes, 1,200 vector constructs, and 300 cell lines have been added to the system, along with 1,500 associated sample locations. Data are stored on a Microsoft SQL Server 2008 installation with a database size of approximately 7\u2005MB. The more than 20 scientists engaged in functional genomics projects were introduced to the system through a one hour feature presentation, which enabled them to use OLF productively. The system was reported to be intuitive, albeit only one user had previous experience in using a LIMS system. Missing functionality considered useful for increased productivity and user convenience, such as handling of barcoded labels, were added to the system subsequently.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Recommended_system_configuration\">Recommended system configuration<\/span><\/h4>\n<p>OLF relies on a database backend for storing sample related data. However, only primitive data types, such as numbers or text fields, are persisted to the database itself, while all documents and files are stored in a folder and merely linked in the database. In this way, we expect a database size of less than 10\u201320\u2005MB for most use cases. For smaller laboratories with less than 20 members, the file-based SQL database that is part of OLF's standalone version is appropriate. Since no significant processing of data is required, OLF is expected to be responsive even on systems with a single CPU core. For larger laboratories, however, we recommend using a system with multiple CPU cores and a dedicated database management system, such as MySQL for efficiently dealing with concurrent access in a responsive manner. Due to its dynamic nature, OLF has a large memory footprint and we strongly recommend providing a minimum of 768\u2005MB of RAM on Linux and 1024\u2005MB on Windows.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Methods\">Methods<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Grails_web-application_framework\">Grails web-application framework<\/span><\/h3>\n<p>We considered the Java based framework Grails to be the most promising candidate for a building a web-application. Grails is a VMWare\/SpringSource product and builds on the company's experience in industry-standard frameworks such as Hibernate or Spring, which also form the core of Grails. In Grails, plug-ins deliver high-quality solutions for non-trivial web application tasks, e.g. database search (Compass and Apache Lucene), spreadsheet im- and export (Apache POI) and a user\/security management (SpringSecurity). Grails embraces the paradigms convention over configuration and separation of concerns to keep the code concise and clean. Furthermore, Grails hides the complexity of data persistence with an object relational modeling technique, which encapsulates all database interactions and models them through Java domain classes. These characteristics allow faster development and integration of new features.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"OpenLabFramework_2\">OpenLabFramework<\/span><\/h3>\n<p>As illustrated in Figure 3, OLF has a modular structure, in which a back-end plug-in provides the necessary base classes, as well as user, project and security management. Content plug-ins can then add arbitrary classes and view templates, and integrate with other plug-ins. All plug-ins are finally merged in the front-end application, which utilizes the scaffolding mechanism of Grails to dynamically create Ajax-driven views for user interaction.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_List_ScientificReports2014_4.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"c014fbf8135e15b5cefd7630ea697b59\"><img alt=\"Fig3 List ScientificReports2014 4.jpg\" src=\"https:\/\/www.limswiki.org\/images\/1\/1c\/Fig3_List_ScientificReports2014_4.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 3. OpenLabFramework is built in a strictly modular fashion.<\/b> A back-end module provides the basic functionality, including project and user management, as well as base classes for other modules. Additional modules extend the base classes and integrate with existing ones. Finally, the front-end module creates views for all defined content and allows for interaction through a responsive web-interface.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>The back-end of OLF introduces two base classes called MasterDataObject and DataObject (Figure 4). MasterDataObjects can be extended by classes representing master data that are maintained by system administrators, e.g. wildtype cell lines or vector systems in the GeneTracker module, or freezers and storage locations in the Storage module. More dynamic content is expressed through DataObject classes, which can be created and modified by regular users, e.g. genes or genetically engineered cell lines in the GeneTracker module, or StorageElements, which contain location data for other DataObject instances, in the StorageModule. This hierarchy makes OLF highly generic, but also allows fine-grained interactions between more specialized classes.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_List_ScientificReports2014_4.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"cebff3bc4a064d0f16596e6406fe4e12\"><img alt=\"Fig4 List ScientificReports2014 4.jpg\" src=\"https:\/\/www.limswiki.org\/images\/f\/f5\/Fig4_List_ScientificReports2014_4.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 4. The back-end provides two classes MasterDataObject (MDO) and DataObject (DO) that are extended by the different modules.<\/b> MDOs can only be created by administrators, whereas DOs can be created by any user. Existing DOs and MDOs can be combined freely by module developers in order to build complex hierarchies.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>OLF strictly follows established patterns found in software architecture. Code is separated into different functional layers according to the model-view-controller pattern. In addition, business logic related code is bundled in service classes and tag libraries to avoid code duplication. Furthermore, OLF introduces the concept of content modules, which can be attached to existing pages. Content modules can either contribute new links to OLF's menu, render additional add-ins or tabs, or provide additional links called operations (Figure 1). By providing a clear structure and suitable interfaces, other developers can thus easily contribute to OLF.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h2>\n<p>Numerous commercial and open-source laboratory information management systems (LIMS) exist today. However, since commercial licenses are expensive and lack the possibility to be adapted to specific needs without additional costs, academic laboratories usually focus on finding an open-source solution to their sample management issues. Moreover, none of the existing solutions seems optimal for all given tasks (Table 2). Naturally, most LIMS are dedicated to a specific field of research and are thus not generally suited for other fields. Some solutions, on the other hand, focus on certain general aspects of laboratory work, such as sample tracking, protocols, or work-flows.\n<\/p><p>OpenLabFramework (OLF) was developed to address the need for an open-source LIMS solution for covering vector constructs and cell line library sample tracking. Acknowledging that many LIMS remain limited to their research domain, we created OLF in a strictly modular and extensible fashion, with dedicated modules for sample tracking, barcoded label printing, and file management. We expect that OLF can be adapted to other research fields and biomaterials with minimal developmental effort by implementing a content module similar to GeneTracker, which is then complemented by plugging in additional features as needed.\n<\/p><p>We built OLF using Grails and its extensive plug-in eco-system. This allows OLF to satisfy basic software development requirements, such as flexibility, reliability and simplicity. The use of a solid framework allows developers to focus on user-specific requirements, as for instance the support for mobile devices, and to keep the application up-to-date, since it will improve together with the underlying framework. The use of Grails, which can be considered the most dynamic and flexible web-application framework available in Java, together with its plug-ins, poses a significant simplification when adding new web-application features. This advantage separates OLF from comparable LIMS, which also embrace the concept of modularity or the use of web-application frameworks.\n<\/p><p>The introduction of OLF allows controlling sample logistics effectively, which is a particular challenge upon movement, turn-over of lab staff, and improper labeling of samples. OLF may further increase productivity by including modern technologies so far disregarded by most other open-source LIMS, such as printing and reading barcode labels. The high degree of automation and standardization that can be achieved by this may substantially reduce user-caused errors in sample assignment. A web-layer for mobile devices provides an additional advantage. In this way, samples can now be removed from physical and virtual storage at the same time, thus limiting the risk of forgetting this step after the work with the sample is completed. As illustrated in Figure 2, the implementation of OLF in a laboratory environment can lead to a significantly more productive work-flow.\n<\/p><p>Finally, unlike most LIMS, OLF is not bound to a specific database or web-container. OLF can be coupled with a large number of database management systems, including non-SQL solutions like MongoDB. If a suitable server is not available, OLF can be installed locally or even be deployed to the cloud with little effort, as demonstrated in our demo application. This flexibility will reduce technical hurdles in the introduction of OLF to a new laboratory.\n<\/p><p>OLF offers efficient and user-friendly management of sample information and location in the field of high-throughput biology and functional genomics. Being extensible, it can be adapted to satisfy additional requirements with little developmental effort. One requirement currently neglected is the extensive integration of additional web tools, which would make OLF more attractive to end-users. Although result data files can be uploaded and linked to samples, we envision that direct interfacing with laboratory equipment would make result data management significantly more convenient. The implementation of RESTful web services could expose OLF data sets and functionality to other tools and information systems. Along with this, the reporting capabilities could be improved, allowing for customized reports, where information from several instances is pooled. This would also help in establishing data analysis directly within OLF or through integration of additional tools (R15). Another important aspect worth considering is that OLF might in some instances require a more fine-grained access to the data. This functionality could be added through additional user roles or access control lists. Finally, the creation of a dedicated app for mobile platforms, such as Android or iOS, would improve the mobile user experience.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>In order to retain an overview over large sample libraries typically found in nowadays laboratories, an efficient system for management and tracking of samples is required. OpenLabFramework (OLF) has been developed with focus on vector construct and cell line libraries. Thanks to its modularity, however, it can be adapted to new scenarios. OLF can be deployed using different database management systems either locally, to a server, or to the cloud. The incorporation of modern technologies, such as mobile devices and printing of barcode labels may increase productivity even further. These properties together may be considered characteristic for a next-generation LIMS and should provide the potential for widespread adaptation.\n<\/p><p>OLF embraces open-source in the hope of attracting not only laboratories in need of a LIMS, but also a community of software developers willing to adapt OLF to new scenarios. We intend to contribute in the future by developing further modules, e.g. for seamless evaluation of experimental data by integration of third party tools. Consequent utilization of community-proven open-source libraries make OLF's backend already highly reliable. With the support of its own community, OLF as a whole is expected to reach the same high quality standard in the future.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Additional_information\">Additional information<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Availability_and_Requirements\">Availability and Requirements<\/span><\/h3>\n<p>Project name: OpenLabFramework\n<\/p><p>URL: <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/github.com\/NanoCAN\/OpenLabFramework\" target=\"_blank\">https:\/\/github.com\/NanoCAN\/OpenLabFramework<\/a>\n<\/p><p>Wiki: <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/github.com\/NanoCAN\/OpenLabFramework\/wiki\" target=\"_blank\">https:\/\/github.com\/NanoCAN\/OpenLabFramework\/wiki<\/a>\n<\/p><p>Demo: <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nanocan.dk\/openlabframework\/demo\" target=\"_blank\">http:\/\/www.nanocan.dk\/openlabframework\/demo<\/a> (user: admin, password: demo0815)\n<\/p><p>Operating system(s): Platform independent\n<\/p><p>Programming language: Java, Groovy, Java-script\n<\/p><p>Other requirements: Java 1.6 or higher, Tomcat 6.0 or higher\n<\/p><p>License: GNU GPL v3\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>This work was supported by the Lundbeckfonden grant for the NanoCAN Center of Excellence in Nanomedicine, the Region Syddanmarks ph.d.-pulje and Forskningspulje, the Fonden Til L\u00e6gevidenskabens Fremme, and co-financed by the INTERREG 4 A-program Syddanmark-Schleswig-K.E.R.N. with funds from The European Regional Development Fund.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Author_information\">Author information<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Affiliations\">Affiliations<\/span><\/h3>\n<p><b>Lundbeckfonden Center of Excellence in Nanomedicine NanoCAN, University of Southern Denmark, Odense, DK<\/b>\n<\/p><p>Markus List, Steffen Schmidt, Jakub Trojnar, Mads Thomassen, Torben A. Kruse & Jan Mollenhauer\n<\/p><p><b>Institute of Molecular Medicin (IMM), University of Southern Denmark, Odense, DK<\/b>\n<\/p><p>Markus List, Steffen Schmidt, Jakub Trojnar & Jan Mollenhauer\n<\/p><p><b>Clinical Institute (CI), University of Southern Denmark, Odense, DK<\/b>\n<\/p><p>Markus List, Mads Thomassen, Torben A. Kruse & Qihua Tan\n<\/p><p><b>Epidemiology, Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark, Odense, DK<\/b>\n<\/p><p>Qihua Tan\n<\/p><p><b>Department of Biochemistry and Molecular Biology (BMB), University of Southern Denmark, Odense, DK<\/b>\n<\/p><p>Jakub Trojnar\n<\/p><p><b>io-consultants GmbH & Co. KG, Heidelberg, DE<\/b>\n<\/p><p>Jochen Thomas\n<\/p><p><b>Department of Mathematics and Computer Science (IMADA), University of Southern Denmark, Odense, DK<\/b>\n<\/p><p>Jan Baumbach\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Contributions\">Contributions<\/span><\/h3>\n<p>M.L. and J.Th. developed the software requirement specification. S.S. and J.Tr. specified requirements specific to the biomedical domain and contributed extensively to bug-tracking and regular testing of OLF. ML implemented the application. M.T., T.K., Q.T., J.B. and J.M. jointly supervised the project, designed graphics and work-flow diagrams. All authors contributed equally to drafting the manuscript. All authors read and approved the final manuscript.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Competing_interests\">Competing interests<\/span><\/h3>\n<p>The authors declare no competing financial interests.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Corresponding_author\">Corresponding author<\/span><\/h3>\n<p>Correspondence to <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/srep04278\/email\/correspondent\/c1\/new\" target=\"_blank\">Markus List<\/a>.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Supplementary_information\">Supplementary information<\/span><\/h2>\n<p><b>PDF files<\/b>\n1.<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/article-assets\/npg\/srep\/2014\/140304\/srep04278\/extref\/srep04278-s1.pdf\" target=\"_blank\">Supplementary Information<\/a>: OpenLabFramework Supplemental Material\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<ol class=\"references\">\n<li id=\"cite_note-Sanchez-VilledaDev03-1\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-Sanchez-VilledaDev03_1-0\" rel=\"external_link\">1.0<\/a><\/sup> <sup><a href=\"#cite_ref-Sanchez-VilledaDev03_1-1\" rel=\"external_link\">1.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sanchez-Villeda, H.; Schroeder, S.; Polacco, M. et al. 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(2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3436699\" target=\"_blank\">\"ProteinTracker: An application for managing protein production and purification\"<\/a>. <i>BMC Research Notes<\/i> <b>5<\/b>: 224. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1756-0500-5-224\" target=\"_blank\">10.1186\/1756-0500-5-224<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3436699\/\" target=\"_blank\">PMC3436699<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22574679\" target=\"_blank\">22574679<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3436699\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3436699<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=ProteinTracker%3A+An+application+for+managing+protein+production+and+purification&rft.jtitle=BMC+Research+Notes&rft.aulast=Ponko%2C+S.C.%3B+Bienvenue%2C+D.&rft.au=Ponko%2C+S.C.%3B+Bienvenue%2C+D.&rft.date=2012&rft.volume=5&rft.pages=224&rft_id=info:doi\/10.1186%2F1756-0500-5-224&rft_id=info:pmc\/PMC3436699&rft_id=info:pmid\/22574679&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC3436699&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-DroitPARPS07-6\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-DroitPARPS07_6-0\" rel=\"external_link\">6.0<\/a><\/sup> <sup><a href=\"#cite_ref-DroitPARPS07_6-1\" rel=\"external_link\">6.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Droit, A.; Hunter, J.M.; Rouleau, M. et al. (2007). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2266781\" target=\"_blank\">\"PARPs database: A LIMS systems for protein-protein interaction data mining or laboratory information management system\"<\/a>. <i>BMC Bioinformatics<\/i> <b>8<\/b>: 483. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2105-8-483\" target=\"_blank\">10.1186\/1471-2105-8-483<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2266781\/\" target=\"_blank\">PMC2266781<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18093328\" target=\"_blank\">18093328<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2266781\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2266781<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=PARPs+database%3A+A+LIMS+systems+for+protein-protein+interaction+data+mining+or+laboratory+information+management+system&rft.jtitle=BMC+Bioinformatics&rft.aulast=Droit%2C+A.%3B+Hunter%2C+J.M.%3B+Rouleau%2C+M.+et+al.&rft.au=Droit%2C+A.%3B+Hunter%2C+J.M.%3B+Rouleau%2C+M.+et+al.&rft.date=2007&rft.volume=8&rft.pages=483&rft_id=info:doi\/10.1186%2F1471-2105-8-483&rft_id=info:pmc\/PMC2266781&rft_id=info:pmid\/18093328&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2266781&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-MorisawaDev06-7\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-MorisawaDev06_7-0\" rel=\"external_link\">7.0<\/a><\/sup> <sup><a href=\"#cite_ref-MorisawaDev06_7-1\" rel=\"external_link\">7.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Morisawa, H.; Hirota, M.; Toda, T. (2006). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1599757\" target=\"_blank\">\"Development of an open source laboratory information management system for 2-D gel electrophoresis-based proteomics workflow\"<\/a>. <i>BMC Bioinformatics<\/i> <b>7<\/b>: 430. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2105-7-430\" target=\"_blank\">10.1186\/1471-2105-7-430<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1599757\/\" target=\"_blank\">PMC1599757<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17018156\" target=\"_blank\">17018156<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1599757\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1599757<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Development+of+an+open+source+laboratory+information+management+system+for+2-D+gel+electrophoresis-based+proteomics+workflow&rft.jtitle=BMC+Bioinformatics&rft.aulast=Morisawa%2C+H.%3B+Hirota%2C+M.%3B+Toda%2C+T.&rft.au=Morisawa%2C+H.%3B+Hirota%2C+M.%3B+Toda%2C+T.&rft.date=2006&rft.volume=7&rft.pages=430&rft_id=info:doi\/10.1186%2F1471-2105-7-430&rft_id=info:pmc\/PMC1599757&rft_id=info:pmid\/17018156&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC1599757&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-HaebelLISA01-8\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-HaebelLISA01_8-0\" rel=\"external_link\">8.0<\/a><\/sup> <sup><a href=\"#cite_ref-HaebelLISA01_8-1\" rel=\"external_link\">8.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Haebel, P.W.; Arcus, V.L.; Baker, E.N.; Metcalf, P. (2001). \"LISA: An intranet-based flexible database for protein crystallography project management\". <i>Acta Crystallographica Section D<\/i> <b>57<\/b> (Pt 9): 1341-1343. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1107%2FS0907444901009295\" target=\"_blank\">10.1107\/S0907444901009295<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/11526339\" target=\"_blank\">11526339<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=LISA%3A+An+intranet-based+flexible+database+for+protein+crystallography+project+management&rft.jtitle=Acta+Crystallographica+Section+D&rft.aulast=Haebel%2C+P.W.%3B+Arcus%2C+V.L.%3B+Baker%2C+E.N.%3B+Metcalf%2C+P.&rft.au=Haebel%2C+P.W.%3B+Arcus%2C+V.L.%3B+Baker%2C+E.N.%3B+Metcalf%2C+P.&rft.date=2001&rft.volume=57&rft.issue=Pt+9&rft.pages=1341-1343&rft_id=info:doi\/10.1107%2FS0907444901009295&rft_id=info:pmid\/11526339&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-TripletTheEnz12-9\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-TripletTheEnz12_9-0\" rel=\"external_link\">9.0<\/a><\/sup> <sup><a href=\"#cite_ref-TripletTheEnz12_9-1\" rel=\"external_link\">9.1<\/a><\/sup> <sup><a href=\"#cite_ref-TripletTheEnz12_9-2\" rel=\"external_link\">9.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Triplet, T.; Butler, G. (2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3353834\" target=\"_blank\">\"The EnzymeTracker: An open-source laboratory information management system for sample tracking\"<\/a>. <i>BMC Bioinformatics<\/i> <b>13<\/b> (15): 1341-1343. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2105-13-15\" target=\"_blank\">10.1186\/1471-2105-13-15<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3353834\/\" target=\"_blank\">PMC3353834<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22280360\" target=\"_blank\">22280360<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3353834\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3353834<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+EnzymeTracker%3A+An+open-source+laboratory+information+management+system+for+sample+tracking&rft.jtitle=BMC+Bioinformatics&rft.aulast=Triplet%2C+T.%3B+Butler%2C+G.&rft.au=Triplet%2C+T.%3B+Butler%2C+G.&rft.date=2012&rft.volume=13&rft.issue=15&rft.pages=1341-1343&rft_id=info:doi\/10.1186%2F1471-2105-13-15&rft_id=info:pmc\/PMC3353834&rft_id=info:pmid\/22280360&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC3353834&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-OlhovskyOpen11-10\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-OlhovskyOpen11_10-0\" rel=\"external_link\">10.0<\/a><\/sup> <sup><a href=\"#cite_ref-OlhovskyOpen11_10-1\" rel=\"external_link\">10.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Olhovsky, M.; Williton, K.; Dai, A.Y. et al. (2011). \"OpenFreezer: A reagent information management software system\". <i>Nature Methods<\/i> <b>8<\/b> (8): 612\u2013613. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fnmeth.1658\" target=\"_blank\">10.1038\/nmeth.1658<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21799493\" target=\"_blank\">21799493<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=OpenFreezer%3A+A+reagent+information+management+software+system&rft.jtitle=Nature+Methods&rft.aulast=Olhovsky%2C+M.%3B+Williton%2C+K.%3B+Dai%2C+A.Y.+et+al.&rft.au=Olhovsky%2C+M.%3B+Williton%2C+K.%3B+Dai%2C+A.Y.+et+al.&rft.date=2011&rft.volume=8&rft.issue=8&rft.pages=612%E2%80%93613&rft_id=info:doi\/10.1038%2Fnmeth.1658&rft_id=info:pmid\/21799493&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-Stocker_iLAP09-11\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-Stocker_iLAP09_11-0\" rel=\"external_link\">11.0<\/a><\/sup> <sup><a href=\"#cite_ref-Stocker_iLAP09_11-1\" rel=\"external_link\">11.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Stocker, G.; Fischer, M.; Rieder, D. et al. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2789074\" target=\"_blank\">\"iLAP: a workflow-driven software for experimental protocol development, data acquisition and analysis\"<\/a>. <i>BMC Bioinformatics<\/i> <b>10<\/b>: 390. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2105-10-390\" target=\"_blank\">10.1186\/1471-2105-10-390<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2789074\/\" target=\"_blank\">PMC2789074<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19941647\" target=\"_blank\">19941647<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2789074\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2789074<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=iLAP%3A+a+workflow-driven+software+for+experimental+protocol+development%2C+data+acquisition+and+analysis&rft.jtitle=BMC+Bioinformatics&rft.aulast=Stocker%2C+G.%3B+Fischer%2C+M.%3B+Rieder%2C+D.+et+al.&rft.au=Stocker%2C+G.%3B+Fischer%2C+M.%3B+Rieder%2C+D.+et+al.&rft.date=2009&rft.volume=10&rft.pages=390&rft_id=info:doi\/10.1186%2F1471-2105-10-390&rft_id=info:pmc\/PMC2789074&rft_id=info:pmid\/19941647&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2789074&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-MeloSIGLa10-12\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-MeloSIGLa10_12-0\" rel=\"external_link\">12.0<\/a><\/sup> <sup><a href=\"#cite_ref-MeloSIGLa10_12-1\" rel=\"external_link\">12.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Melo, Alexandre; Alessandra Faria-Campos; Daiane M DeLaat; Rodrigo Keller; Vin\u00edcius Abreu; S\u00e9rgio Campos (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3045801\" target=\"_blank\">\"SIGLa: an adaptable LIMS for multiple laboratories\"<\/a>. <i>BMC Genomics<\/i> <b>11<\/b> (Suppl 5): S8. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2164-11-S5-S8\" target=\"_blank\">10.1186\/1471-2164-11-S5-S8<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3045801\/\" target=\"_blank\">PMC3045801<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21210974\" target=\"_blank\">21210974<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3045801\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3045801<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=SIGLa%3A+an+adaptable+LIMS+for+multiple+laboratories&rft.jtitle=BMC+Genomics&rft.aulast=Melo%2C+Alexandre%3B+Alessandra+Faria-Campos%3B+Daiane+M+DeLaat%3B+Rodrigo+Keller%3B+Vin%C3%ADcius+Abreu%3B+S%C3%A9rgio+Campos&rft.au=Melo%2C+Alexandre%3B+Alessandra+Faria-Campos%3B+Daiane+M+DeLaat%3B+Rodrigo+Keller%3B+Vin%C3%ADcius+Abreu%3B+S%C3%A9rgio+Campos&rft.date=2010&rft.volume=11&rft.issue=Suppl+5&rft.pages=S8&rft_id=info:doi\/10.1186%2F1471-2164-11-S5-S8&rft_id=info:pmc\/PMC3045801&rft_id=info:pmid\/21210974&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC3045801&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-BurgarellaMicro05-13\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-BurgarellaMicro05_13-0\" rel=\"external_link\">13.0<\/a><\/sup> <sup><a href=\"#cite_ref-BurgarellaMicro05_13-1\" rel=\"external_link\">13.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Burgarella, S.; Cattaneo, D.; Pinciroli, F.; Masseroli, M. (2005). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1866379\" target=\"_blank\">\"MicroGen: a MIAME compliant web system for microarray experiment information and workflow management\"<\/a>. <i>BMC Bioinformatics<\/i> <b>6<\/b> (Suppl 4): S6. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2105-6-S4-S6\" target=\"_blank\">10.1186\/1471-2105-6-S4-S6<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1866379\/\" target=\"_blank\">PMC1866379<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16351755\" target=\"_blank\">16351755<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1866379\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1866379<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=MicroGen%3A+a+MIAME+compliant+web+system+for+microarray+experiment+information+and+workflow+management&rft.jtitle=BMC+Bioinformatics&rft.aulast=Burgarella%2C+S.%3B+Cattaneo%2C+D.%3B+Pinciroli%2C+F.%3B+Masseroli%2C+M.&rft.au=Burgarella%2C+S.%3B+Cattaneo%2C+D.%3B+Pinciroli%2C+F.%3B+Masseroli%2C+M.&rft.date=2005&rft.volume=6&rft.issue=Suppl+4&rft.pages=S6&rft_id=info:doi\/10.1186%2F1471-2105-6-S4-S6&rft_id=info:pmc\/PMC1866379&rft_id=info:pmid\/16351755&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC1866379&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-KrestyaninovaASys09-14\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-KrestyaninovaASys09_14-0\" rel=\"external_link\">14.0<\/a><\/sup> <sup><a href=\"#cite_ref-KrestyaninovaASys09_14-1\" rel=\"external_link\">14.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Krestyaninova, M.; Zarins, A.; Viksna, J. et al. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2759553\" target=\"_blank\">\"A system for information management in biomedical studies \u2013 SIMBioMS\"<\/a>. <i>Bioinformatics<\/i> <b>25<\/b> (20): 2768-2769. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fbioinformatics%2Fbtp420\" target=\"_blank\">10.1093\/bioinformatics\/btp420<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2759553\/\" target=\"_blank\">PMC2759553<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19633095\" target=\"_blank\">19633095<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2759553\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2759553<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+system+for+information+management+in+biomedical+studies+%E2%80%93+SIMBioMS&rft.jtitle=Bioinformatics&rft.aulast=Krestyaninova%2C+M.%3B+Zarins%2C+A.%3B+Viksna%2C+J.+et+al.&rft.au=Krestyaninova%2C+M.%3B+Zarins%2C+A.%3B+Viksna%2C+J.+et+al.&rft.date=2009&rft.volume=25&rft.issue=20&rft.pages=2768-2769&rft_id=info:doi\/10.1093%2Fbioinformatics%2Fbtp420&rft_id=info:pmc\/PMC2759553&rft_id=info:pmid\/19633095&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2759553&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-TruongMolab11-15\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-TruongMolab11_15-0\" rel=\"external_link\">15.0<\/a><\/sup> <sup><a href=\"#cite_ref-TruongMolab11_15-1\" rel=\"external_link\">15.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Truong, C.V.C.; Groeneveld, L.F.; Morgenstern, B.; Groeneveld, E. (2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3268772\" target=\"_blank\">\"MolabIS - An integrated information system for storing and managing molecular genetics data\"<\/a>. <i>BMC Bioinformatics<\/i> <b>12<\/b>: 425. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2105-12-425\" target=\"_blank\">10.1186\/1471-2105-12-425<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3268772\/\" target=\"_blank\">PMC3268772<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22040322\" target=\"_blank\">22040322<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3268772\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3268772<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=MolabIS+-+An+integrated+information+system+for+storing+and+managing+molecular+genetics+data&rft.jtitle=BMC+Bioinformatics&rft.aulast=Truong%2C+C.V.C.%3B+Groeneveld%2C+L.F.%3B+Morgenstern%2C+B.%3B+Groeneveld%2C+E.&rft.au=Truong%2C+C.V.C.%3B+Groeneveld%2C+L.F.%3B+Morgenstern%2C+B.%3B+Groeneveld%2C+E.&rft.date=2011&rft.volume=12&rft.pages=425&rft_id=info:doi\/10.1186%2F1471-2105-12-425&rft_id=info:pmc\/PMC3268772&rft_id=info:pmid\/22040322&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC3268772&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-MollenhauerDavid10-16\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-MollenhauerDavid10_16-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mollenhauer, J.; Stamou, D.; Flyvbjerg, A. et al. (2010). \"David versus Goliath\". <i>Nanomedicine<\/i> <b>6<\/b> (4): 504\u2013509. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.nano.2010.04.002\" target=\"_blank\">10.1016\/j.nano.2010.04.002<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20417315\" target=\"_blank\">20417315<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=David+versus+Goliath&rft.jtitle=Nanomedicine&rft.aulast=Mollenhauer%2C+J.%3B+Stamou%2C+D.%3B+Flyvbjerg%2C+A.+et+al.&rft.au=Mollenhauer%2C+J.%3B+Stamou%2C+D.%3B+Flyvbjerg%2C+A.+et+al.&rft.date=2010&rft.volume=6&rft.issue=4&rft.pages=504%E2%80%93509&rft_id=info:doi\/10.1016%2Fj.nano.2010.04.002&rft_id=info:pmid\/20417315&rfr_id=info:sid\/en.wikipedia.org:Journal:Efficient_sample_tracking_with_OpenLabFramework\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. In Table 2, checkmarks and Xs were replaced with Ys and Ns. The \"Methods\" section has also been moved from the end to a more logical position before the Discussion and Conclusion.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192207\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.491 seconds\nReal time usage: 0.521 seconds\nPreprocessor visited node count: 15252\/1000000\nPreprocessor generated node count: 30248\/1000000\nPost\u2010expand include size: 137362\/2097152 bytes\nTemplate argument size: 43846\/2097152 bytes\nHighest expansion depth: 18\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 469.041 1 - -total\n 79.37% 372.287 1 - Template:Reflist\n 72.86% 341.766 16 - Template:Cite_journal\n 69.73% 327.063 16 - Template:Citation\/core\n 13.30% 62.396 1 - Template:Infobox_journal_article\n 12.75% 59.789 1 - Template:Infobox\n 12.34% 57.876 43 - Template:Citation\/identifier\n 7.63% 35.794 80 - Template:Infobox\/row\n 4.35% 20.389 97 - Template:Hide_in_print\n 4.06% 19.021 16 - Template:Citation\/make_link\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:7936-0!*!0!!en!5!* and timestamp 20181214192207 and revision id 23800\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Efficient_sample_tracking_with_OpenLabFramework\">https:\/\/www.limswiki.org\/index.php\/Journal:Efficient_sample_tracking_with_OpenLabFramework<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","241f9c1d4812074890e77322c80e615c_images":["https:\/\/www.limswiki.org\/images\/4\/49\/Fig1_List_ScientificReports2014_4.jpg","https:\/\/www.limswiki.org\/images\/3\/31\/Fig2_List_ScientificReports2014_4.jpg","https:\/\/www.limswiki.org\/images\/1\/1c\/Fig3_List_ScientificReports2014_4.jpg","https:\/\/www.limswiki.org\/images\/f\/f5\/Fig4_List_ScientificReports2014_4.jpg"],"241f9c1d4812074890e77322c80e615c_timestamp":1544815327,"8192951e8c0a01c0f0c395c213ebbe59_type":"article","8192951e8c0a01c0f0c395c213ebbe59_title":"Diagnostic time in digital pathology: A comparative study on 400 cases (Vodovnik 2016)","8192951e8c0a01c0f0c395c213ebbe59_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases","8192951e8c0a01c0f0c395c213ebbe59_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:Diagnostic time in digital pathology: A comparative study on 400 cases\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nDiagnostic time in digital pathology: A comparative study on 400 casesJournal\n \nJournal of Pathology InformaticsAuthor(s)\n \nVodovnik, AleksandarAuthor affiliation(s)\n \nForde Central HospitalPrimary contact\n \nEmail: N\/AYear published\n \n2016Volume and issue\n \n7Page(s)\n \n4DOI\n \n10.4103\/2153-3539.175377ISSN\n \n2153-3539Distribution license\n \nCreative Commons Attribution-NonCommercial-ShareAlike 3.0 UnportedWebsite\n \nhttp:\/\/www.jpathinformatics.orgDownload\n \nhttp:\/\/www.jpathinformatics.org\/temp\/JPatholInform714-5222773_143027.pdf (PDF)\n\nContents\n\n1 Abstract \n2 Introduction \n3 Materials and methods \n4 Results \n5 Discussion \n6 Conclusions \n7 Acknowledgements \n8 Financial support and sponsorship \n9 Conflicts of interest \n10 References \n11 Notes \n\n\n\nAbstract \nBackground: Numerous validation studies in digital pathology confirmed its value as a diagnostic tool. However, a longer time to diagnosis than traditional microscopy has been seen as a significant barrier to the routine use of digital pathology. As a part of our validation study, we compared a digital and microscopic diagnostic time in the routine diagnostic setting. \nMaterials and methods: One senior staff pathologist reported 400 consecutive cases in histology, nongynecological, and fine needle aspiration cytology (20 sessions, 20 cases\/session), over 4 weeks. Complex, difficult, and rare cases were excluded from the study to reduce the bias. A primary diagnosis was digital, followed by traditional microscopy, six months later, with only request forms available for both. Microscopic slides were scanned at \u00d720, digital images accessed through the fully integrated laboratory information management system (LIMS) and viewed in the image viewer on double 23\u201d displays. A median broadband speed was 299 Mbps. A diagnostic time was measured from the point slides were made available to the point diagnosis was made or additional investigations were deemed necessary, recorded independently in minutes\/session and compared. \nResults: A digital diagnostic time was 1841 and microscopic 1956 min; digital being shorter than microscopic in 13 sessions. Four sessions with shorter microscopic diagnostic time included more cases requiring extensive use of magnifications over \u00d720. Diagnostic time was similar in three sessions. \nConclusions: A diagnostic time in digital pathology can be shorter than traditional microscopy in the routine diagnostic setting, with adequate and stable network speeds, fully integrated LIMS and double displays as default parameters. This also related to better ergonomics, larger viewing field, and absence of physical slide handling, with effects on both diagnostic and nondiagnostic time. Differences with previous studies included a design, image size, number of cases, specimen type, network speed, and participant's level of confidence and experience in digital reporting. Further advancements in working stations and gained experience in digital reporting are expected to improve diagnostic time and widen routine applications of digital pathology.\nKeywords: Diagnostic time, digital pathology, turnaround\n\nIntroduction \nNumerous validation studies in digital pathology confirmed its value as a diagnostic tool.[1][2][3] Main advantages for wider implementation of digital pathology, in comparison to traditional microscopy, include better ergonomics, immediate access to slides, and distance reporting. However, a longer time to diagnosis than traditional microscopy has been seen as a significant barrier to the routine use of digital pathology, especially in early studies.[4] Advances in working stations led to the narrowing or equaling of the diagnostic time gap and further improvements of the digital diagnostic experience, in experimental studies on a limited number of cases.[5][6][7][8] As a part of our validation study, we compared digital and microscopic diagnostic time in the routine diagnostic setting. Technical issues were seen as potential obstacles and shortened turnaround, through the faster digital diagnostic time, desired benefits.\n\nMaterials and methods \nOne senior staff pathologist reported 400 consecutive cases (1396 slides) in histology, nongynecological and fine needle aspiration cytology, by means of digital pathology and traditional microscopy (20 sessions and 20 cases\/session), over four weeks [Figure 1]. \n\n\n\n\n\n\n\n\n\n Figure 1. Case workload reported in this study\n\n\n\nComplex, difficult, and rare cases were excluded from the study to reduce the bias, as pathologists often remember those cases for a long time. This group nevertheless included one complex, one difficult, and two rare cases. A primary diagnosis was digital, used for clinical management, followed by traditional microscopy, six months later. Only request forms were available for both primary and secondary diagnosis. Microscopic slides were prepared by standard techniques and routinely stained hematoxylin-eosin. In addition, upper gastrointestinal diagnostic biopsies were stained Alcian blue\/periodic acid-Schiff and liver core biopsies Masson trichrome\/iron\/reticulin, respectively. Cytological slides were routinely stained either Romanowsky or Romanowsky\/Papanicolaou and were not prescreened. Microscopic slides were scanned at \u00d720 using Scan Scope AT Turbo digital scanner (Leica). Digital images were accessed through the fully integrated laboratory information management system (LIMS) SymPathy (Tieto) and viewed in ImageScope (Leica) on a desktop PC with double displays [Table 1] using a broadband connection [Table 2]. \n\n\n\n\n\n\n\n Table 1. Technical specification for equipment used in digital reporting\n\n\nMake and model\n\nDell OptiPlex 7010\n\n\nOperative system\n\nWindows 7 Enterprise 64 bit\n\n\nProcessor\n\ni3-3240M 3.40 GHz\n\n\nDisplay size and resolution\n\nDouble 23\", 1920x1200\n\n\nRead-only memory\n\n500 GB\n\n\nRandom access memory\n\n8 GB\n\n\n\n\n\n\n\n\n\n Table 2. Broadband speed (Mbps) - variation, median and average\n\n\n\n\n Variation\n\n Median\n\n Average\n\n\nDownload speed\n\n150\u2013400\n\n299\n\n250\n\n\nUpload speed\n\n35\u2013150\n\n55\n\n50\n\n\n\nA microscopic diagnosis was made on an Eclipse 80i light microscope (Nikon). Turnaround refers in this study to diagnostic (slide evaluation) and nondiagnostic time (dictation, sign off, access to clinical information, and previous history, etc.). A diagnostic time was measured from the point slides were made available to the point diagnosis was made or additional investigations were deemed necessary, recorded independently in minutes\/session and compared. It did not include interruptions into the reporting sessions. An unstructured sessional log was recorded to identify factors contributing to improved diagnostic time. Broadband speeds were automatically recorded every 30 min into digital reporting sessions and analyzed.\n\nResults \nA total digital diagnostic time was shorter than microscopic, 1841 versus 1956 min, respectively. Distributions of digital and microscopic diagnostic time per session are shown in [Table 3] and [Figure 2]. \n\n\n\n\n\n\n\n Table 3. Diagnostic time per session (min) - variation, median and average\n\n\n\n\n Variation\n\n Median\n\n Average\n\n\nDigital\n\n79\u2013106\n\n93\n\n92.05\n\n\nMicroscopic\n\n84\u2013109\n\n99.5\n\n97.8\n\n\n\n\n\n\n\n\n\n\n\n\n Figure 2. Distribution of diagnostic time\n\n\n\nA digital diagnostic time was shorter than microscopic in 13 sessions. Four sessions with shorter microscopic diagnostic time included more cases requiring extensive use of magnifications over \u00d720 [Table 4]. \n\n\n\n\n\n\n\n Table 4. Main reasons for more extensive use of magnification over \u00d720\n\n\n Reason\n\n Diagnostic problem\n\n\nLow bacterial load\n\nPresence of Helicobacter pylori\n\n\nLow tumour load\n\nPresence of nonsmall cell cancer\n\n\nNuclear features\n\nLymphoma versus carcinoma\n\n\n\nThe diagnostic time was similar in three sessions. Data analysis from the unstructured sessional log identified factors contributing most to the shorter digital diagnostic time [Table 5]. Differences with previous studies are listed in [Table 6].\n\n\n\n\n\n\n\n Table 5. Factors contributing to shortened digital diagnostic time\n\n\n Factors\n\n Benefits\n\n\nErgonomics\n\nLess tiring reporting sessions\n\n\nLarger viewing field\n\nLesser number of viewing fields\n\n\nAbsence of physical slide handling\n\nFaster switching between slides\/magnifications; reduced checking slides against requisitions\n\n\n\n\n\n\n\n\n\n Table 6. Differences with previous studies in digital reporting\n\n\n Variables\n\n Previous studies\n\n Present study\n\n\nDesign\n\nExperimental\n\nRoutine\n\n\nNetwork speed\n\nVariable\n\nStable\n\n\nImage size\n\nScan at x20 and x40\n\nScan at x20\n\n\nNumber of cases\n\nLow\n\nHigh\n\n\nSpecimen type\n\nOrgan-specific\n\nMixed\n\n\nExperience\n\nVariable\n\nLong\n\n\n\nDiscussion \nAlthough numerous validation studies in digital pathology confirmed its value as a diagnostic tool, a longer time to diagnosis than traditional microscopy has been seen as the main obstacle to wider implementation of primary digital diagnostics. Early works showed up to 60% longer time to diagnosis in digital pathology comparing to traditional microscopy.[4] Recent advances in digital working stations have shown slightly longer or similar digital diagnostic time to traditional microscopy in experimental studies on a limited number of cases or slides, involving though multiple pathologists. A high-resolution array of 28 computer screens allowed, after just a few minutes familiarization, tasks to be performed as quickly and confidently as a microscope.[5]\nAssessing the effect of display resolution, Randell et al. showed that time to diagnosis and time to first target were faster on the microscope than on the single and three-screen displays, viewing axillary lymph node slides.[6] Although there was no significant difference between the microscope and the three-screen display in time to first target, the time taken on the single-screen display was significantly higher than that on the microscope. The results suggested that a digital pathology workstation with an increased number of pixels may allow the quicker initial slide overview, however, in the case of a detailed slide search, increased resolution may not offer any additional benefits. Double 23\u201d displays have been used in our study, one for LIMS and the other for image viewer, seen as a minimal requirement. In our validation of digital pathology, we have tested multiple displays available on the market, including ultra-high definition (4K), and purchased the ones mentioned above as the best value for money and benefits to digital diagnostics.[9]\nIn their further studies, Randell et al. achieved a similar time to diagnosis for the conventional and virtual microscope. Although the mean slide viewing time was also similar, participants spent a significantly greater proportion of the total task time viewing slides and revisited slides more often, or there was a significant difference in the mean magnification used between the two technologies, with participants working at a higher level of magnification on the virtual microscope.[7][8] This may be related to the level of confidence and experience in digital reporting, and was not observed by the reporting pathologist in this study.\nMore exact comparison of results was found to be limited due to differences with previous studies in design, image size, network speed, case number, case workload, and experience in digital reporting, all affecting digital diagnostic time [Table 6]. Similar to previous studies, multiple displays were seen as an advantage in our study as well. In contrast, our study was conducted in the routine diagnostic setting with a varied case workload and high case numbers. In addition to the wash-out period of 6 months, those are seen as strengths of this study. As adoption of primary digital reporting relays on individual preferences and learning curves for each pathologist, a number of participating pathologists has not been seen as an issue in this study.\nA shorter digital diagnostic time in our study has been achieved in the routine diagnostic setting with stable and adequate network speeds, full integration of digital scanner with LIMS and double displays as default parameters. As previously shown, an instant upload of digital images in the image viewer has been achieved at 20 Mbps.[9] Average, median and variation of download and upload network speeds were both well above and accordingly regarded as stable. Correlations between digital and microscopic diagnosis were 99% for the reporting pathologist (unpublished data) and therefore not specifically addressed in this study. One percent of cases (six) showed a minor discordance (without clinical implications), with no cases showing a major discordance (with clinical implications) in that study, which was fully compliant to the College of American Pathologists recommendation.[10]\nImprovements in digital diagnostic time also related to better ergonomics, larger viewing field, and absence of physical slide handling. Better ergonomics in the digital reporting setting, with less eye and wrist fatigue, has been recognized as an important advantage comparing to traditional microscopy, allowing longer uninterrupted diagnostic sessions to be carried out.[2][9] Larger viewing field allowed completion of slide viewing in lesser number of fields, subject to magnifications used, for both small diagnostic biopsies, and large resections specimens. In the absence of physical slide handling, switching between slides and magnifications was nearly instant and superior to the traditional microscopy, as the focus was maintained throughout. The need for double checking of slides against request forms by pathologist has almost completely disappeared, as only digital slides belonging to the patient could be linked to the patient in LIMS. A number of specimens per sample could be still simultaneously checked by pathologist against digital slides as double displays were used, one for the LIMS and the other for viewing of digital slides.\nSlide viewing patterns among pathologist with long experience in the digital review have been recently studied.[11] Combinations of directed and cover panning with dip-zooming were also experienced in this study as superior to traditional microscopy. That especially goes for chipping specimens from, for example, prostate, urinary bladder, or endometrium. The whole slide could be viewed at lower magnification in one field and dip-zoomed to the area of interest. The other advantage, comparing to traditional microscopy, is that images appear in the viewer fit to window at magnifications up to \u00d74, depending on the specimen size. That often allowed an instant diagnosis in the very first viewing field for smaller biopsies, shortening diagnostic time substantially.\nAn average digital and microscopic diagnostic time in cytology was similar in this study. A majority of specimens were prepared using liquid-based cytology techniques with remaining traditional smears being done by pathologists. This way we were able to ascertain a high quality of slides with limited areas to scan and evaluate, contributing to the effective digital diagnostics and minimizing scanning issues. The routine use of a scanning magnification \u00d720 and a digital zoom to achieve \u00d740 caused no issues in this study.\nTurnaround comprises of a diagnostic and nondiagnostic time. A shorter digital diagnostic time in this study amounted to additional 250 cases a year, for the reporting pathologist, as savings in the diagnostic time only. The nondiagnostic time has not been exactly measured due to logistical reason with the routine diagnostic setting and difficulties to repeat the same nondiagnostic variables during the secondary microscopic sessions. However, a consolidation of multiple tasks in digital reporting systems was seen as a contributory factor in shortening of the nondiagnostic time as well, especially in dictation, sign off and access to the previous history, as previously shown.[9][12] Observations from this study suggest savings of at least 10% in the nondiagnostic time comparing to the traditional microscopy diagnostic setting amounting roughly to additional 350 cases a year. Extra savings in diagnostic and nondiagnostic time could be alternatively used for consultation, administration or teaching, depending on departmental needs or individual preferences of pathologists.\nFour sessions with a shorter microscopic diagnostic time included more gastric, lung, and lymph node biopsies comparing to the rest of the sessions. Those required more extensive use of magnifications \u00d740 due to low bacterial or tumor loads and to ascertain nuclear features. Although all cases in this group were reported using a digital zoom to achieve magnifications \u00d740, it took a longer time to make a confident diagnosis due to digital zoom's focusing imperfections. As a result of this study, we are considering to routinely scan all minute diagnostic biopsies with queries of malignancy at \u00d740 instead.\n\nConclusions \nDigital reporting systems allow today multiple advances in working settings comparing to the traditional microscopy. It is up to individual pathologists to discover their own ways to take the advantage of this new working environment to the benefit of the patient and hospital budget.\nA shorter diagnostic time in digital pathology comparing with traditional microscopy can be achieved in the routine diagnostic setting with adequate and stable network speeds, fully integrated LIMS and double displays as default parameters, in addition to better ergonomics, larger viewing field, and absence of physical slide handling, with effects on the both diagnostic and nondiagnostic time. Further advancements in working stations and gained experience in digital reporting are expected to improve the diagnostic time and widen applications of digital pathology.\n\nAcknowledgements \nThis study was supported by Digital Pathology Project at our institution, sponsored by the Health Authority-West (Helse vest), project number 795421. The author is grateful to the departmental laboratory staff for their support and encouragement, as well as members of the project group and the regional IT Department (HVIKT) for their valuable contributions to the success of our digital pathology project.\n\nFinancial support and sponsorship \nHealth Authority West grant 795421.\n\nConflicts of interest \nThere are no conflicts of interest.\n\nReferences \n\n\n\u2191 Stathonikos, N.; Veta, M.; Huisman, A.; van Diest, P.J. (2013). \"Going fully digital: Perspective of a Dutch academic pathology lab\". Journal of Pathology Informatics 4: 15. doi:10.4103\/2153-3539.114206. PMC PMC3709427. PMID 23858390. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3709427 .   \n\n\u2191 2.0 2.1 Thorstenson, S.; Molin, J.; Lundstr\u00f6m, C. (2014). \"Implementation of large-scale routine diagnostics using whole slide imaging in Sweden: Digital pathology experiences 2006-2013\". Journal of Pathology Informatics 5: 14. doi:10.4103\/2153-3539.129452. PMC PMC4023034. PMID 24843825. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4023034 .   \n\n\u2191 Bauer, T.W.; Slaw, R.J. (2014). \"Validating whole-slide imaging for consultation diagnoses in surgical pathology\". Archives of Pathology and Laboratory Medicine 138 (11): 1459-65. doi:10.5858\/arpa.2013-0541-OA. PMID 24840034.   \n\n\u2191 4.0 4.1 Treanor, D.; Quirke, P. (2007). \"The virtual slide and conventional microscope \u2014 A direct comparison of their diagnostic efficiency\". The Journal of Pathology 213: 7a.   \n\n\u2191 5.0 5.1 Treanor, D.; Jordan-Owers, N.; Hodrien, J. et al.. \"Virtual reality Powerwall versus conventional microscope for viewing pathology slides: An experimental comparison\". Histopathology 55 (3): 294-300. doi:10.1111\/j.1365-2559.2009.03389.x. 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(2015). \"Distance reporting in digital pathology: A study on 950 cases\". Journal of Pathology Informatics 6: 18. doi:10.4103\/2153-3539.156168. PMC PMC4421888. PMID 25969793. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4421888 .   \n\n\u2191 Pantanowitz, L.; Sinard, J.H.; Henricks, W.H. et al.. \"Validating whole slide imaging for diagnostic purposes in pathology: Guideline from the College of American Pathologists Pathology and Laboratory Quality Center\". Archives of Pathology and Laboratory Medicine 137 (12): 1710-22. doi:10.5858\/arpa.2013-0093-CP. PMID 23634907.   \n\n\u2191 Molin, J.; Fjeld, M.; Mello-Thoms, C.; Lundstr\u00f6m, C.. \"Slide navigation patterns among pathologists with long experience of digital review\". Histopathology 67 (2): 185-92. doi:10.1111\/his.12629. PMID 25487230.   \n\n\u2191 Randell R.; Ruddle, R.A.; Quirke, P. et al. (2012). \"Working at the microscope: Analysis of the activities involved in diagnostic pathology\". Histopathology 60 (3): 504-10. doi:10.1111\/j.1365-2559.2011.04090.x. PMC 22176210. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=22176210 .   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. Numbers 0 through 9 were changed from numerals to words when appropriate.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\">https:\/\/www.limswiki.org\/index.php\/Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on pathology informatics\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 2 April 2016, at 20:01.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 716 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","8192951e8c0a01c0f0c395c213ebbe59_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_Diagnostic_time_in_digital_pathology_A_comparative_study_on_400_cases skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Diagnostic time in digital pathology: A comparative study on 400 cases<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p><b>Background:<\/b> Numerous validation studies in digital pathology confirmed its value as a diagnostic tool. However, a longer time to diagnosis than traditional microscopy has been seen as a significant barrier to the routine use of digital pathology. As a part of our validation study, we compared a digital and microscopic diagnostic time in the routine diagnostic setting. \n<\/p><p><b>Materials and methods:<\/b> One senior staff pathologist reported 400 consecutive cases in histology, nongynecological, and fine needle aspiration cytology (20 sessions, 20 cases\/session), over 4 weeks. Complex, difficult, and rare cases were excluded from the study to reduce the bias. A primary diagnosis was digital, followed by traditional microscopy, six months later, with only request forms available for both. Microscopic slides were scanned at \u00d720, digital images accessed through the fully integrated <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" target=\"_blank\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">laboratory information management system<\/a> (LIMS) and viewed in the image viewer on double 23\u201d displays. A median broadband speed was 299 Mbps. A diagnostic time was measured from the point slides were made available to the point diagnosis was made or additional investigations were deemed necessary, recorded independently in minutes\/session and compared. \n<\/p><p><b>Results:<\/b> A digital diagnostic time was 1841 and microscopic 1956 min; digital being shorter than microscopic in 13 sessions. Four sessions with shorter microscopic diagnostic time included more cases requiring extensive use of magnifications over \u00d720. Diagnostic time was similar in three sessions. \n<\/p><p><b>Conclusions:<\/b> A diagnostic time in digital pathology can be shorter than traditional microscopy in the routine diagnostic setting, with adequate and stable network speeds, fully integrated LIMS and double displays as default parameters. This also related to better ergonomics, larger viewing field, and absence of physical slide handling, with effects on both diagnostic and nondiagnostic time. Differences with previous studies included a design, image size, number of cases, specimen type, network speed, and participant's level of confidence and experience in digital reporting. Further advancements in working stations and gained experience in digital reporting are expected to improve diagnostic time and widen routine applications of digital pathology.\n<\/p><p><b>Keywords:<\/b> Diagnostic time, digital pathology, turnaround\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>Numerous validation studies in digital pathology confirmed its value as a diagnostic tool.<sup id=\"rdp-ebb-cite_ref-StathonikosGoing13_1-0\" class=\"reference\"><a href=\"#cite_note-StathonikosGoing13-1\" rel=\"external_link\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-ThorstensonImp14_2-0\" class=\"reference\"><a href=\"#cite_note-ThorstensonImp14-2\" rel=\"external_link\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-BauerValid14_3-0\" class=\"reference\"><a href=\"#cite_note-BauerValid14-3\" rel=\"external_link\">[3]<\/a><\/sup> Main advantages for wider implementation of digital pathology, in comparison to traditional microscopy, include better ergonomics, immediate access to slides, and distance reporting. However, a longer time to diagnosis than traditional microscopy has been seen as a significant barrier to the routine use of digital pathology, especially in early studies.<sup id=\"rdp-ebb-cite_ref-TreanorTheVirt07_4-0\" class=\"reference\"><a href=\"#cite_note-TreanorTheVirt07-4\" rel=\"external_link\">[4]<\/a><\/sup> Advances in working stations led to the narrowing or equaling of the diagnostic time gap and further improvements of the digital diagnostic experience, in experimental studies on a limited number of cases.<sup id=\"rdp-ebb-cite_ref-TreanorVirt09_5-0\" class=\"reference\"><a href=\"#cite_note-TreanorVirt09-5\" rel=\"external_link\">[5]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-RandellEffect15_6-0\" class=\"reference\"><a href=\"#cite_note-RandellEffect15-6\" rel=\"external_link\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-RandellDiag14_7-0\" class=\"reference\"><a href=\"#cite_note-RandellDiag14-7\" rel=\"external_link\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-RandellVirtual13_8-0\" class=\"reference\"><a href=\"#cite_note-RandellVirtual13-8\" rel=\"external_link\">[8]<\/a><\/sup> As a part of our validation study, we compared digital and microscopic diagnostic time in the routine diagnostic setting. Technical issues were seen as potential obstacles and shortened turnaround, through the faster digital diagnostic time, desired benefits.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Materials_and_methods\">Materials and methods<\/span><\/h2>\n<p>One senior staff pathologist reported 400 consecutive cases (1396 slides) in histology, nongynecological and fine needle aspiration cytology, by means of digital pathology and traditional microscopy (20 sessions and 20 cases\/session), over four weeks [Figure 1]. \n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Vodovnik_JofPathInformatics2016_7.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"7248c2d813225abc1efaf6a2d4c9ee4f\"><img alt=\"Fig1 Vodovnik JofPathInformatics2016 7.jpg\" src=\"https:\/\/www.limswiki.org\/images\/b\/b6\/Fig1_Vodovnik_JofPathInformatics2016_7.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 1.<\/b> Case workload reported in this study<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>Complex, difficult, and rare cases were excluded from the study to reduce the bias, as pathologists often remember those cases for a long time. This group nevertheless included one complex, one difficult, and two rare cases. A primary diagnosis was digital, used for clinical management, followed by traditional microscopy, six months later. Only request forms were available for both primary and secondary diagnosis. Microscopic slides were prepared by standard techniques and routinely stained hematoxylin-eosin. In addition, upper gastrointestinal diagnostic biopsies were stained Alcian blue\/periodic acid-Schiff and liver core biopsies Masson trichrome\/iron\/reticulin, respectively. Cytological slides were routinely stained either Romanowsky or Romanowsky\/Papanicolaou and were not prescreened. Microscopic slides were scanned at \u00d720 using Scan Scope AT Turbo digital scanner (Leica). Digital images were accessed through the fully integrated laboratory information management system (LIMS) SymPathy (Tieto) and viewed in ImageScope (Leica) on a desktop PC with double displays [Table 1] using a broadband connection [Table 2]. \n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\" colspan=\"2\"> <b>Table 1.<\/b> Technical specification for equipment used in digital reporting\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Make and model<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Dell OptiPlex 7010\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Operative system<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Windows 7 Enterprise 64 bit\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Processor<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">i3-3240M 3.40 GHz\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Display size and resolution<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Double 23\", 1920x1200\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Read-only memory<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">500 GB\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Random access memory<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8 GB\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\" colspan=\"4\"> <b>Table 2.<\/b> Broadband speed (Mbps) - variation, median and average\n<\/td><\/tr>\n<tr>\n<th>\n<\/th>\n<th> Variation\n<\/th>\n<th> Median\n<\/th>\n<th> Average\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Download speed\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">150\u2013400\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">299\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">250\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Upload speed\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">35\u2013150\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">55\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">50\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>A microscopic diagnosis was made on an Eclipse 80i light microscope (Nikon). Turnaround refers in this study to diagnostic (slide evaluation) and nondiagnostic time (dictation, sign off, access to clinical <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" target=\"_blank\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a>, and previous history, etc.). A diagnostic time was measured from the point slides were made available to the point diagnosis was made or additional investigations were deemed necessary, recorded independently in minutes\/session and compared. It did not include interruptions into the reporting sessions. An unstructured sessional log was recorded to identify factors contributing to improved diagnostic time. Broadband speeds were automatically recorded every 30 min into digital reporting sessions and analyzed.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h2>\n<p>A total digital diagnostic time was shorter than microscopic, 1841 versus 1956 min, respectively. Distributions of digital and microscopic diagnostic time per session are shown in [Table 3] and [Figure 2]. \n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\" colspan=\"4\"> <b>Table 3.<\/b> Diagnostic time per session (min) - variation, median and average\n<\/td><\/tr>\n<tr>\n<th>\n<\/th>\n<th> Variation\n<\/th>\n<th> Median\n<\/th>\n<th> Average\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Digital\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">79\u2013106\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">93\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">92.05\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Microscopic\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">84\u2013109\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">99.5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">97.8\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Vodovnik_JofPathInformatics2016_7.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"9f147c3790ca1c892dd24836a5c32e6b\"><img alt=\"Fig2 Vodovnik JofPathInformatics2016 7.jpg\" src=\"https:\/\/www.limswiki.org\/images\/2\/2d\/Fig2_Vodovnik_JofPathInformatics2016_7.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 2.<\/b> Distribution of diagnostic time<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>A digital diagnostic time was shorter than microscopic in 13 sessions. Four sessions with shorter microscopic diagnostic time included more cases requiring extensive use of magnifications over \u00d720 [Table 4]. \n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\" colspan=\"2\"> <b>Table 4.<\/b> Main reasons for more extensive use of magnification over \u00d720\n<\/td><\/tr>\n<tr>\n<th> Reason\n<\/th>\n<th> Diagnostic problem\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Low bacterial load\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Presence of <i>Helicobacter pylori<\/i>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Low tumour load\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Presence of nonsmall cell cancer\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Nuclear features\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Lymphoma versus carcinoma\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>The diagnostic time was similar in three sessions. Data analysis from the unstructured sessional log identified factors contributing most to the shorter digital diagnostic time [Table 5]. Differences with previous studies are listed in [Table 6].\n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\" colspan=\"2\"> <b>Table 5.<\/b> Factors contributing to shortened digital diagnostic time\n<\/td><\/tr>\n<tr>\n<th> Factors\n<\/th>\n<th> Benefits\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ergonomics\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Less tiring reporting sessions\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Larger viewing field\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Lesser number of viewing fields\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Absence of physical slide handling\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Faster switching between slides\/magnifications; reduced checking slides against requisitions\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"padding-left:10px; padding-right:10px;\" colspan=\"3\"> <b>Table 6.<\/b> Differences with previous studies in digital reporting\n<\/td><\/tr>\n<tr>\n<th> Variables\n<\/th>\n<th> Previous studies\n<\/th>\n<th> Present study\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Design\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Experimental\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Routine\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Network speed\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Variable\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Stable\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Image size\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Scan at x20 and x40\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Scan at x20\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Number of cases\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Low\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">High\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Specimen type\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Organ-specific\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Mixed\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Experience\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Variable\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Long\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h2><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h2>\n<p>Although numerous validation studies in digital pathology confirmed its value as a diagnostic tool, a longer time to diagnosis than traditional microscopy has been seen as the main obstacle to wider implementation of primary digital diagnostics. Early works showed up to 60% longer time to diagnosis in digital pathology comparing to traditional microscopy.<sup id=\"rdp-ebb-cite_ref-TreanorTheVirt07_4-1\" class=\"reference\"><a href=\"#cite_note-TreanorTheVirt07-4\" rel=\"external_link\">[4]<\/a><\/sup> Recent advances in digital working stations have shown slightly longer or similar digital diagnostic time to traditional microscopy in experimental studies on a limited number of cases or slides, involving though multiple pathologists. A high-resolution array of 28 computer screens allowed, after just a few minutes familiarization, tasks to be performed as quickly and confidently as a microscope.<sup id=\"rdp-ebb-cite_ref-TreanorVirt09_5-1\" class=\"reference\"><a href=\"#cite_note-TreanorVirt09-5\" rel=\"external_link\">[5]<\/a><\/sup>\n<\/p><p>Assessing the effect of display resolution, Randell <i>et al.<\/i> showed that time to diagnosis and time to first target were faster on the microscope than on the single and three-screen displays, viewing axillary lymph node slides.<sup id=\"rdp-ebb-cite_ref-RandellEffect15_6-1\" class=\"reference\"><a href=\"#cite_note-RandellEffect15-6\" rel=\"external_link\">[6]<\/a><\/sup> Although there was no significant difference between the microscope and the three-screen display in time to first target, the time taken on the single-screen display was significantly higher than that on the microscope. The results suggested that a digital pathology workstation with an increased number of pixels may allow the quicker initial slide overview, however, in the case of a detailed slide search, increased resolution may not offer any additional benefits. Double 23\u201d displays have been used in our study, one for LIMS and the other for image viewer, seen as a minimal requirement. In our validation of digital pathology, we have tested multiple displays available on the market, including ultra-high definition (4K), and purchased the ones mentioned above as the best value for money and benefits to digital diagnostics.<sup id=\"rdp-ebb-cite_ref-VodovnikDist15_9-0\" class=\"reference\"><a href=\"#cite_note-VodovnikDist15-9\" rel=\"external_link\">[9]<\/a><\/sup>\n<\/p><p>In their further studies, Randell <i>et al.<\/i> achieved a similar time to diagnosis for the conventional and virtual microscope. Although the mean slide viewing time was also similar, participants spent a significantly greater proportion of the total task time viewing slides and revisited slides more often, or there was a significant difference in the mean magnification used between the two technologies, with participants working at a higher level of magnification on the virtual microscope.<sup id=\"rdp-ebb-cite_ref-RandellDiag14_7-1\" class=\"reference\"><a href=\"#cite_note-RandellDiag14-7\" rel=\"external_link\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-RandellVirtual13_8-1\" class=\"reference\"><a href=\"#cite_note-RandellVirtual13-8\" rel=\"external_link\">[8]<\/a><\/sup> This may be related to the level of confidence and experience in digital reporting, and was not observed by the reporting pathologist in this study.\n<\/p><p>More exact comparison of results was found to be limited due to differences with previous studies in design, image size, network speed, case number, case workload, and experience in digital reporting, all affecting digital diagnostic time [Table 6]. Similar to previous studies, multiple displays were seen as an advantage in our study as well. In contrast, our study was conducted in the routine diagnostic setting with a varied case workload and high case numbers. In addition to the wash-out period of 6 months, those are seen as strengths of this study. As adoption of primary digital reporting relays on individual preferences and learning curves for each pathologist, a number of participating pathologists has not been seen as an issue in this study.\n<\/p><p>A shorter digital diagnostic time in our study has been achieved in the routine diagnostic setting with stable and adequate network speeds, full integration of digital scanner with LIMS and double displays as default parameters. As previously shown, an instant upload of digital images in the image viewer has been achieved at 20 Mbps.<sup id=\"rdp-ebb-cite_ref-VodovnikDist15_9-1\" class=\"reference\"><a href=\"#cite_note-VodovnikDist15-9\" rel=\"external_link\">[9]<\/a><\/sup> Average, median and variation of download and upload network speeds were both well above and accordingly regarded as stable. Correlations between digital and microscopic diagnosis were 99% for the reporting pathologist (unpublished data) and therefore not specifically addressed in this study. One percent of cases (six) showed a minor discordance (without clinical implications), with no cases showing a major discordance (with clinical implications) in that study, which was fully compliant to the College of American Pathologists recommendation.<sup id=\"rdp-ebb-cite_ref-PantanowitzValid13_10-0\" class=\"reference\"><a href=\"#cite_note-PantanowitzValid13-10\" rel=\"external_link\">[10]<\/a><\/sup>\n<\/p><p>Improvements in digital diagnostic time also related to better ergonomics, larger viewing field, and absence of physical slide handling. Better ergonomics in the digital reporting setting, with less eye and wrist fatigue, has been recognized as an important advantage comparing to traditional microscopy, allowing longer uninterrupted diagnostic sessions to be carried out.<sup id=\"rdp-ebb-cite_ref-ThorstensonImp14_2-1\" class=\"reference\"><a href=\"#cite_note-ThorstensonImp14-2\" rel=\"external_link\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-VodovnikDist15_9-2\" class=\"reference\"><a href=\"#cite_note-VodovnikDist15-9\" rel=\"external_link\">[9]<\/a><\/sup> Larger viewing field allowed completion of slide viewing in lesser number of fields, subject to magnifications used, for both small diagnostic biopsies, and large resections specimens. In the absence of physical slide handling, switching between slides and magnifications was nearly instant and superior to the traditional microscopy, as the focus was maintained throughout. The need for double checking of slides against request forms by pathologist has almost completely disappeared, as only digital slides belonging to the patient could be linked to the patient in LIMS. A number of specimens per sample could be still simultaneously checked by pathologist against digital slides as double displays were used, one for the LIMS and the other for viewing of digital slides.\n<\/p><p>Slide viewing patterns among pathologist with long experience in the digital review have been recently studied.<sup id=\"rdp-ebb-cite_ref-MolinSlide15_11-0\" class=\"reference\"><a href=\"#cite_note-MolinSlide15-11\" rel=\"external_link\">[11]<\/a><\/sup> Combinations of directed and cover panning with dip-zooming were also experienced in this study as superior to traditional microscopy. That especially goes for chipping specimens from, for example, prostate, urinary bladder, or endometrium. The whole slide could be viewed at lower magnification in one field and dip-zoomed to the area of interest. The other advantage, comparing to traditional microscopy, is that images appear in the viewer fit to window at magnifications up to \u00d74, depending on the specimen size. That often allowed an instant diagnosis in the very first viewing field for smaller biopsies, shortening diagnostic time substantially.\n<\/p><p>An average digital and microscopic diagnostic time in cytology was similar in this study. A majority of specimens were prepared using liquid-based cytology techniques with remaining traditional smears being done by pathologists. This way we were able to ascertain a high quality of slides with limited areas to scan and evaluate, contributing to the effective digital diagnostics and minimizing scanning issues. The routine use of a scanning magnification \u00d720 and a digital zoom to achieve \u00d740 caused no issues in this study.\n<\/p><p>Turnaround comprises of a diagnostic and nondiagnostic time. A shorter digital diagnostic time in this study amounted to additional 250 cases a year, for the reporting pathologist, as savings in the diagnostic time only. The nondiagnostic time has not been exactly measured due to logistical reason with the routine diagnostic setting and difficulties to repeat the same nondiagnostic variables during the secondary microscopic sessions. However, a consolidation of multiple tasks in digital reporting systems was seen as a contributory factor in shortening of the nondiagnostic time as well, especially in dictation, sign off and access to the previous history, as previously shown.<sup id=\"rdp-ebb-cite_ref-VodovnikDist15_9-3\" class=\"reference\"><a href=\"#cite_note-VodovnikDist15-9\" rel=\"external_link\">[9]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-RandellWork12_12-0\" class=\"reference\"><a href=\"#cite_note-RandellWork12-12\" rel=\"external_link\">[12]<\/a><\/sup> Observations from this study suggest savings of at least 10% in the nondiagnostic time comparing to the traditional microscopy diagnostic setting amounting roughly to additional 350 cases a year. Extra savings in diagnostic and nondiagnostic time could be alternatively used for consultation, administration or teaching, depending on departmental needs or individual preferences of pathologists.\n<\/p><p>Four sessions with a shorter microscopic diagnostic time included more gastric, lung, and lymph node biopsies comparing to the rest of the sessions. Those required more extensive use of magnifications \u00d740 due to low bacterial or tumor loads and to ascertain nuclear features. Although all cases in this group were reported using a digital zoom to achieve magnifications \u00d740, it took a longer time to make a confident diagnosis due to digital zoom's focusing imperfections. As a result of this study, we are considering to routinely scan all minute diagnostic biopsies with queries of malignancy at \u00d740 instead.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>Digital reporting systems allow today multiple advances in working settings comparing to the traditional microscopy. It is up to individual pathologists to discover their own ways to take the advantage of this new working environment to the benefit of the patient and hospital budget.\n<\/p><p>A shorter diagnostic time in digital pathology comparing with traditional microscopy can be achieved in the routine diagnostic setting with adequate and stable network speeds, fully integrated LIMS and double displays as default parameters, in addition to better ergonomics, larger viewing field, and absence of physical slide handling, with effects on the both diagnostic and nondiagnostic time. Further advancements in working stations and gained experience in digital reporting are expected to improve the diagnostic time and widen applications of digital pathology.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>This study was supported by Digital Pathology Project at our institution, sponsored by the Health Authority-West (Helse vest), project number 795421. The author is grateful to the departmental laboratory staff for their support and encouragement, as well as members of the project group and the regional IT Department (HVIKT) for their valuable contributions to the success of our digital pathology project.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Financial_support_and_sponsorship\">Financial support and sponsorship<\/span><\/h2>\n<p>Health Authority West grant 795421.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conflicts_of_interest\">Conflicts of interest<\/span><\/h2>\n<p>There are no conflicts of interest.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<ol class=\"references\">\n<li id=\"cite_note-StathonikosGoing13-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-StathonikosGoing13_1-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Stathonikos, N.; Veta, M.; Huisman, A.; van Diest, P.J. 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(2014). \"Validating whole-slide imaging for consultation diagnoses in surgical pathology\". <i>Archives of Pathology and Laboratory Medicine<\/i> <b>138<\/b> (11): 1459-65. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5858%2Farpa.2013-0541-OA\" target=\"_blank\">10.5858\/arpa.2013-0541-OA<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24840034\" target=\"_blank\">24840034<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Validating+whole-slide+imaging+for+consultation+diagnoses+in+surgical+pathology&rft.jtitle=Archives+of+Pathology+and+Laboratory+Medicine&rft.aulast=Bauer%2C+T.W.%3B+Slaw%2C+R.J.&rft.au=Bauer%2C+T.W.%3B+Slaw%2C+R.J.&rft.date=2014&rft.volume=138&rft.issue=11&rft.pages=1459-65&rft_id=info:doi\/10.5858%2Farpa.2013-0541-OA&rft_id=info:pmid\/24840034&rfr_id=info:sid\/en.wikipedia.org:Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-TreanorTheVirt07-4\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-TreanorTheVirt07_4-0\" rel=\"external_link\">4.0<\/a><\/sup> <sup><a href=\"#cite_ref-TreanorTheVirt07_4-1\" rel=\"external_link\">4.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Treanor, D.; Quirke, P. (2007). \"The virtual slide and conventional microscope \u2014 A direct comparison of their diagnostic efficiency\". <i>The Journal of Pathology<\/i> <b>213<\/b>: 7a.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+virtual+slide+and+conventional+microscope+%E2%80%94+A+direct+comparison+of+their+diagnostic+efficiency&rft.jtitle=The+Journal+of+Pathology&rft.aulast=Treanor%2C+D.%3B+Quirke%2C+P.&rft.au=Treanor%2C+D.%3B+Quirke%2C+P.&rft.date=2007&rft.volume=213&rft.pages=7a&rfr_id=info:sid\/en.wikipedia.org:Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-TreanorVirt09-5\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-TreanorVirt09_5-0\" rel=\"external_link\">5.0<\/a><\/sup> <sup><a href=\"#cite_ref-TreanorVirt09_5-1\" rel=\"external_link\">5.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Treanor, D.; Jordan-Owers, N.; Hodrien, J. et al.. \"Virtual reality Powerwall versus conventional microscope for viewing pathology slides: An experimental comparison\". <i>Histopathology<\/i> <b>55<\/b> (3): 294-300. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fj.1365-2559.2009.03389.x\" target=\"_blank\">10.1111\/j.1365-2559.2009.03389.x<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19723144\" target=\"_blank\">19723144<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Virtual+reality+Powerwall+versus+conventional+microscope+for+viewing+pathology+slides%3A+An+experimental+comparison&rft.jtitle=Histopathology&rft.aulast=Treanor%2C+D.%3B+Jordan-Owers%2C+N.%3B+Hodrien%2C+J.+et+al.&rft.au=Treanor%2C+D.%3B+Jordan-Owers%2C+N.%3B+Hodrien%2C+J.+et+al.&rft.volume=55&rft.issue=3&rft.pages=294-300&rft_id=info:doi\/10.1111%2Fj.1365-2559.2009.03389.x&rft_id=info:pmid\/19723144&rfr_id=info:sid\/en.wikipedia.org:Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-RandellEffect15-6\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-RandellEffect15_6-0\" rel=\"external_link\">6.0<\/a><\/sup> <sup><a href=\"#cite_ref-RandellEffect15_6-1\" rel=\"external_link\">6.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Randell, R.; Ambepitiya, T.; Mello-Thoms, C. et al.. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4305057\" target=\"_blank\">\"Effect of display resolution on time to diagnosis with virtual pathology slides in a systematic search task\"<\/a>. <i>Journal of Digital Imaging<\/i> <b>28<\/b> (1): 68\u201376. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs10278-014-9726-8\" target=\"_blank\">10.1007\/s10278-014-9726-8<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4305057\/\" target=\"_blank\">PMC4305057<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25128321\" target=\"_blank\">25128321<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4305057\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4305057<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Effect+of+display+resolution+on+time+to+diagnosis+with+virtual+pathology+slides+in+a+systematic+search+task&rft.jtitle=Journal+of+Digital+Imaging&rft.aulast=Randell%2C+R.%3B+Ambepitiya%2C+T.%3B+Mello-Thoms%2C+C.+et+al.&rft.au=Randell%2C+R.%3B+Ambepitiya%2C+T.%3B+Mello-Thoms%2C+C.+et+al.&rft.volume=28&rft.issue=1&rft.pages=68%E2%80%9376&rft_id=info:doi\/10.1007%2Fs10278-014-9726-8&rft_id=info:pmc\/PMC4305057&rft_id=info:pmid\/25128321&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC4305057&rfr_id=info:sid\/en.wikipedia.org:Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-RandellDiag14-7\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-RandellDiag14_7-0\" rel=\"external_link\">7.0<\/a><\/sup> <sup><a href=\"#cite_ref-RandellDiag14_7-1\" rel=\"external_link\">7.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Randell, R.; Ruddle, R.A., Thomas, R.G. et al.. \"Diagnosis of major cancer resection specimens with virtual slides: Impact of a novel digital pathology workstation\". <i>Human Pathology<\/i> <b>45<\/b> (10): 2101\u20136. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.humpath.2014.06.017\" target=\"_blank\">10.1016\/j.humpath.2014.06.017<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25128229\" target=\"_blank\">25128229<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Diagnosis+of+major+cancer+resection+specimens+with+virtual+slides%3A+Impact+of+a+novel+digital+pathology+workstation&rft.jtitle=Human+Pathology&rft.aulast=Randell%2C+R.%3B+Ruddle%2C+R.A.%2C+Thomas%2C+R.G.+et+al.&rft.au=Randell%2C+R.%3B+Ruddle%2C+R.A.%2C+Thomas%2C+R.G.+et+al.&rft.volume=45&rft.issue=10&rft.pages=2101%E2%80%936&rft_id=info:doi\/10.1016%2Fj.humpath.2014.06.017&rft_id=info:pmid\/25128229&rfr_id=info:sid\/en.wikipedia.org:Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-RandellVirtual13-8\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-RandellVirtual13_8-0\" rel=\"external_link\">8.0<\/a><\/sup> <sup><a href=\"#cite_ref-RandellVirtual13_8-1\" rel=\"external_link\">8.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Randell, R.; Ruddle, R.A., Mello-Thoms, C. et al.. \"Virtual reality microscope versus conventional microscope regarding time to diagnosis: An experimental study\". <i>Histopathology<\/i> <b>62<\/b> (2): 351-8. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fj.1365-2559.2012.04323.x\" target=\"_blank\">10.1111\/j.1365-2559.2012.04323.x<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22882289\" target=\"_blank\">22882289<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Virtual+reality+microscope+versus+conventional+microscope+regarding+time+to+diagnosis%3A+An+experimental+study&rft.jtitle=Histopathology&rft.aulast=Randell%2C+R.%3B+Ruddle%2C+R.A.%2C+Mello-Thoms%2C+C.+et+al.&rft.au=Randell%2C+R.%3B+Ruddle%2C+R.A.%2C+Mello-Thoms%2C+C.+et+al.&rft.volume=62&rft.issue=2&rft.pages=351-8&rft_id=info:doi\/10.1111%2Fj.1365-2559.2012.04323.x&rft_id=info:pmid\/22882289&rfr_id=info:sid\/en.wikipedia.org:Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-VodovnikDist15-9\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-VodovnikDist15_9-0\" rel=\"external_link\">9.0<\/a><\/sup> <sup><a href=\"#cite_ref-VodovnikDist15_9-1\" rel=\"external_link\">9.1<\/a><\/sup> <sup><a href=\"#cite_ref-VodovnikDist15_9-2\" rel=\"external_link\">9.2<\/a><\/sup> <sup><a href=\"#cite_ref-VodovnikDist15_9-3\" rel=\"external_link\">9.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Vodovnik, A. (2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4421888\" target=\"_blank\">\"Distance reporting in digital pathology: A study on 950 cases\"<\/a>. <i>Journal of Pathology Informatics<\/i> <b>6<\/b>: 18. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2F2153-3539.156168\" target=\"_blank\">10.4103\/2153-3539.156168<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4421888\/\" target=\"_blank\">PMC4421888<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25969793\" target=\"_blank\">25969793<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4421888\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4421888<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Distance+reporting+in+digital+pathology%3A+A+study+on+950+cases&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Vodovnik%2C+A.&rft.au=Vodovnik%2C+A.&rft.date=2015&rft.volume=6&rft.pages=18&rft_id=info:doi\/10.4103%2F2153-3539.156168&rft_id=info:pmc\/PMC4421888&rft_id=info:pmid\/25969793&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC4421888&rfr_id=info:sid\/en.wikipedia.org:Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-PantanowitzValid13-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-PantanowitzValid13_10-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Pantanowitz, L.; Sinard, J.H.; Henricks, W.H. et al.. \"Validating whole slide imaging for diagnostic purposes in pathology: Guideline from the College of American Pathologists Pathology and Laboratory Quality Center\". <i>Archives of Pathology and Laboratory Medicine<\/i> <b>137<\/b> (12): 1710-22. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5858%2Farpa.2013-0093-CP\" target=\"_blank\">10.5858\/arpa.2013-0093-CP<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23634907\" target=\"_blank\">23634907<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Validating+whole+slide+imaging+for+diagnostic+purposes+in+pathology%3A+Guideline+from+the+College+of+American+Pathologists+Pathology+and+Laboratory+Quality+Center&rft.jtitle=Archives+of+Pathology+and+Laboratory+Medicine&rft.aulast=Pantanowitz%2C+L.%3B+Sinard%2C+J.H.%3B+Henricks%2C+W.H.+et+al.&rft.au=Pantanowitz%2C+L.%3B+Sinard%2C+J.H.%3B+Henricks%2C+W.H.+et+al.&rft.volume=137&rft.issue=12&rft.pages=1710-22&rft_id=info:doi\/10.5858%2Farpa.2013-0093-CP&rft_id=info:pmid\/23634907&rfr_id=info:sid\/en.wikipedia.org:Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-MolinSlide15-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-MolinSlide15_11-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Molin, J.; Fjeld, M.; Mello-Thoms, C.; Lundstr\u00f6m, C.. \"Slide navigation patterns among pathologists with long experience of digital review\". <i>Histopathology<\/i> <b>67<\/b> (2): 185-92. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fhis.12629\" target=\"_blank\">10.1111\/his.12629<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25487230\" target=\"_blank\">25487230<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Slide+navigation+patterns+among+pathologists+with+long+experience+of+digital+review&rft.jtitle=Histopathology&rft.aulast=Molin%2C+J.%3B+Fjeld%2C+M.%3B+Mello-Thoms%2C+C.%3B+Lundstr%C3%B6m%2C+C.&rft.au=Molin%2C+J.%3B+Fjeld%2C+M.%3B+Mello-Thoms%2C+C.%3B+Lundstr%C3%B6m%2C+C.&rft.volume=67&rft.issue=2&rft.pages=185-92&rft_id=info:doi\/10.1111%2Fhis.12629&rft_id=info:pmid\/25487230&rfr_id=info:sid\/en.wikipedia.org:Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-RandellWork12-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-RandellWork12_12-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Randell R.; Ruddle, R.A.; Quirke, P. et al. (2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=22176210\" target=\"_blank\">\"Working at the microscope: Analysis of the activities involved in diagnostic pathology\"<\/a>. <i>Histopathology<\/i> <b>60<\/b> (3): 504-10. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fj.1365-2559.2011.04090.x\" target=\"_blank\">10.1111\/j.1365-2559.2011.04090.x<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/22176210\/\" target=\"_blank\">22176210<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=22176210\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=22176210<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Working+at+the+microscope%3A+Analysis+of+the+activities+involved+in+diagnostic+pathology&rft.jtitle=Histopathology&rft.aulast=Randell+R.%3B+Ruddle%2C+R.A.%3B+Quirke%2C+P.+et+al.&rft.au=Randell+R.%3B+Ruddle%2C+R.A.%3B+Quirke%2C+P.+et+al.&rft.date=2012&rft.volume=60&rft.issue=3&rft.pages=504-10&rft_id=info:doi\/10.1111%2Fj.1365-2559.2011.04090.x&rft_id=info:pmc\/22176210&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3D22176210&rfr_id=info:sid\/en.wikipedia.org:Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. Numbers 0 through 9 were changed from numerals to words when appropriate.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192207\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.392 seconds\nReal time usage: 0.416 seconds\nPreprocessor visited node count: 11396\/1000000\nPreprocessor generated node count: 28674\/1000000\nPost\u2010expand include size: 94122\/2097152 bytes\nTemplate argument size: 30374\/2097152 bytes\nHighest expansion depth: 18\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 385.936 1 - -total\n 77.13% 297.662 1 - Template:Reflist\n 70.32% 271.384 12 - Template:Cite_journal\n 66.86% 258.019 12 - Template:Citation\/core\n 16.50% 63.695 1 - Template:Infobox_journal_article\n 15.85% 61.156 1 - Template:Infobox\n 9.63% 37.154 26 - Template:Citation\/identifier\n 9.33% 35.993 80 - Template:Infobox\/row\n 4.13% 15.958 12 - Template:Citation\/make_link\n 3.52% 13.568 57 - Template:Hide_in_print\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:8505-0!*!0!!en!5!* and timestamp 20181214192206 and revision id 24890\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases\">https:\/\/www.limswiki.org\/index.php\/Journal:Diagnostic_time_in_digital_pathology:_A_comparative_study_on_400_cases<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","8192951e8c0a01c0f0c395c213ebbe59_images":["https:\/\/www.limswiki.org\/images\/b\/b6\/Fig1_Vodovnik_JofPathInformatics2016_7.jpg","https:\/\/www.limswiki.org\/images\/2\/2d\/Fig2_Vodovnik_JofPathInformatics2016_7.jpg"],"8192951e8c0a01c0f0c395c213ebbe59_timestamp":1544815326,"54f8c03773fbcda29fa23c857f6a1159_type":"article","54f8c03773fbcda29fa23c857f6a1159_title":"Custom software development for use in a clinical laboratory (Sinard et al. 2012)","54f8c03773fbcda29fa23c857f6a1159_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Custom_software_development_for_use_in_a_clinical_laboratory","54f8c03773fbcda29fa23c857f6a1159_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:Custom software development for use in a clinical laboratory\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nCustom software development for use in a clinical laboratoryJournal\n \nJournal of Pathology InformaticsAuthor(s)\n \nSinard, John H.; Gershkovich, PeterAuthor affiliation(s)\n \nYale University School of MedicinePrimary contact\n \nEmail: Available with log-inYear published\n \n2012Volume and issue\n \n3Page(s)\n \n44DOI\n \n10.4103\/2153-3539.104906ISSN\n \n2153-3539Distribution license\n \nCreative Commons Attribution-NonCommercial-ShareAlike 3.0 UnportedWebsite\n \nhttp:\/\/www.jpathinformatics.orgDownload\n \nhttp:\/\/www.jpathinformatics.org\/temp\/JPatholInform3144-4659481_125634.pdf (PDF)\n\nContents\n\n1 Abstract \n2 Introduction \n\n2.1 Facing unmet needs \n\n\n3 Our experience \n4 Buy versus build \n5 Custom software development process \n\n5.1 Functional specification \n5.2 Technical specification \n5.3 Software development \n5.4 Validation \n5.5 Solution deployment \n5.6 Updates and enhancements \n5.7 Project leadership \n\n\n6 Conclusion \n\n6.1 Source of support \n6.2 Conflict of interest \n\n\n7 References \n8 Notes \n\n\n\nAbstract \nIn-house software development for use in a clinical laboratory is a controversial issue. Many of the objections raised are based on outdated software development practices, an exaggeration of the risks involved, and an underestimation of the benefits that can be realized. Buy versus build analyses typically do not consider total costs of ownership, and unfortunately decisions are often made by people who are not directly affected by the workflow obstacles or benefits that result from those decisions. We have been developing custom software for clinical use for over a decade, and this article presents our perspective on this practice. A complete analysis of the decision to develop or purchase must ultimately examine how the end result will mesh with the departmental workflow, and custom-developed solutions typically can have the greater positive impact on efficiency and productivity, substantially altering the decision balance sheet. Involving the end-users in preparation of the functional specifications is crucial to the success of the process. A large development team is not needed, and even a single programmer can develop significant solutions. Many of the risks associated with custom development can be mitigated by a well-structured development process, use of open-source tools, and embracing an agile development philosophy. In-house solutions have the significant advantage of being adaptable to changing departmental needs, contributing to efficient and higher quality patient care.\nKeywords: Buy versus build, clinical use, custom software, in-house development, open source\n\nIntroduction \nFacing unmet needs \nComputer software is an integral part of the day-to-day operation of any clinical laboratory. The major nidus for this activity is the laboratory information system (LIS), typically a suite of integrated modules purchased from a single vendor and designed specifically for the operation of the laboratory. LISs have matured substantially over the past few decades, providing greater operational efficiency and improving patient safety.\nYet, even the most advanced LISs do not fully meet the needs of every laboratory. Although some labs may be able to function adequately on their LIS, larger labs and labs providing specialty services typically can identify information management needs which are not met by their LIS. This is because LIS vendors build their software to meet the needs common to the majority of the labs in their current or intended client base rather than to meet the needs of a particular lab, and every lab has some unique needs due to their size, subtleties of their local environment, people, and the clinical focus of their clients. Thus, a needed functionality is lacking, either because it does not exist at all in the LIS, or because it exists in a way that does not mesh well with the workflow in the lab.\nWhen the LIS functionality falls short of an identified need, labs have a choice: (1) make do with what they have, perhaps adjusting their workflow to accommodate; (2) contract with the LIS vendor to add the needed functionality to their LIS, or to modify it to meet their workflow needs; (3) purchase third-party software which meets the need, (4) develop their own custom software in-house, or (5) purchase a new LIS. Purchasing a new LIS is a huge undertaking and outside of the scope of this discussion. In fact, most labs choose to go with option 1. There can be many ways to accomplish a task in the lab, and labs can adapt to what their LIS is able to do. If the need is great and funds can be identified, option 2 may be chosen. Having your LIS vendor develop integrated customizations assures compatibility with the rest of the LIS, but this can be an expensive and time-consuming process. Nonetheless, LIS vendors rely on at least some clients choosing this option because this funds enhancements to their product. When laboratory science or the regulatory environment creates a general need, the client with the lowest threshold, greatest need, and available capital funds the development of the solution with their vendor. This client has the advantage of dictating how the workflow for the new feature will be designed. After delivery and testing (and payment), the vendor typically incorporates the new feature into a subsequent version of the LIS software, either as a free enhancement or available for an additional charge.\nThird-party solutions can be a good option, and certainly should be investigated. If your lab has an unmet need, others probably have a similar need. There are a number of smaller companies that are more nimble than the major LIS vendors and that can respond more quickly to a need and provide a solution. The less specific the need is to pathology (e.g., transcription, image acquisition), the more likely it is that there will be multiple solutions from which to choose. If the solution can operate independent of the LIS, there are no integration concerns. If it needs to be integrated, the company may be able to handle it themselves, unless modifications are needed to the LIS system, in which case the third-party company will then likely have to enter into some sort of agreement with the LIS vendor. There are many examples of successful third-party solutions, the most common of which is \"middleware\" in the clinical laboratories, which manages communication between analytical instruments and the LIS.\nHowever, if the need is novel or specific for your environment, third-party products that adequately meet that need are often simply not available. In this situation, in-house custom software development may be the best solution.\n\nOur experience \nAt our institution, the pathology department provides anatomic pathology services only (laboratory medicine is a separate department). We have our own Pathology Informatics Unit that provides both operational services (i.e., information technology services) and software development. We also have three other full-time faculty members with academic informatics programs, but they are not involved in the software development for clinical use. Our clinical development team has developed a variety of clinical applications that are used every day in our anatomic pathology practice. Some of these solutions are integrated into and\/or interact with our LIS, and some are standalone solutions. Our development team consists of three people. One is a pathologist, who also has other significant clinical and administrative needs and thus spends only about 20% of his time on software development. His primary role is in specification development and in programming the department's LIS to interact with the custom software (we have a unique arrangement without LIS vendor which allows us to introduce our own customizations into the commercial software, which was nicely designed to allow for this process). Another developer handles the user interface creation (according to the provided specifications) and also handles deployment, user training, and initial support of the custom applications. The third developer spends approximately two-thirds of his time on development, predominantly the business logic of the standalone components of the application, with the other third spent on management of the operational informatics unit in the department. Thus, in total, this represents about 1.6 FTEs (full-time equivalents) of true development resources. Our LIS is Cerner CoPathPlus. Our standalone components are developed in Java, predominantly as web applications.\nOver the past several years, solutions we have developed and deployed include: Digital image file management[1], scanned document file management[2], dictation\/transcription management[3], an outreach support system for orders and report delivery, an outreach client interface system, a repetitive task scheduling engine[4], frozen section management and diagnosis communication to operating rooms[5], histology asset tracking[6][7], trainee diagnosis tracking and evaluation[8], and numerous databases to support trainee interviewing and recruitment, graduate trainee tracking, computer hardware tracking, research histology, and graphics services billing. This article is based on our collective experience with this development and deployment process.\n\nBuy versus build \nMedical institutions operate around a number of philosophies, some codified in actual policies, but most driven by the experiences and\/or preferences of the institutional leadership. In the information technology (IT) departments, one of the most prevalent dichotomies is the preference to buy or build: When an unmet IT need arises, does one buy a commercially available solution or invest in building\/developing a custom solution? Although there is a lot of software commercially available, it is generally not designed for some of the specialty medical uses and may not mesh well with the existing workflow. In many environments, the task of assessing the suitability of available software to meet a specific need is often relegated to IT staff who are not that familiar with the clinical workflow. A solution is purchased and installed which does not fit quite right. Since the \"off-the-shelf\" software is generally not modifiable by the end-user, departments then find themselves adjusting their workflow to match what the software can do. Advocates for the \"build\" philosophy argue that computers are a tool that should be adapted to the user's workflow rather than dictating a particular workflow to its users.\nAdvocates for the \"buy\" philosophy raise a number of common objections to development of software in-house. These, along with counter arguments, are listed in [Table 1]. In addressing any unmet software need, it is always prudent to explore what solutions might be commercially available, either through your LIS vendor or from a third-party. There is a lot of software available commercially from a large number of vendors. How \"thorough\" of an investigation one does depends, of course, on the need and potential benefits, since exploring options can be time-consuming. If your need is unique, however, there may simply be nothing available which comes close. We experienced that when we developed the specifications for our Frozen Section Management and Diagnosis Communication software.[5] The buy versus build cost\/benefit analysis needs to consider the true cost of ownership, not simply the difference between the purchase cost and the development cost. On the buy side, one must include the costs of installing and setting up the new software, included in the cost of most large vendor offerings, but sometimes an additional charge from smaller vendors. Are there additional hardware costs associated with the new software, like workstation upgrades? Are there expenses associated with integrating the new software into your workflow, including any workflow changes and perhaps personnel changes? Does the solution require purchasing specific consumables such as a particular vendor's labels, cassettes, or slides? There may also be subsequent annual support costs, which often run 22-25% of the initial purchase price. Collaborating with your LIS vendor to develop the solution as part of the LIS is an option, but can be expensive, and there will almost certainly be annual support cost increases. Additionally, the vendor will be limited by the technology used to develop the LIS, often technology that is a decade old. Determining the cost of developing software in-house can be difficult, but it usually comes down to people and time - the faster you need the software completed, the more people it may take. The more people you hire, the more expensive it is, and then there is the issue of what are you going to do with those people after the software has been developed? (This is discussed further later.)\n\n\n\n\n\n\n\n\n\n Table 1: Buy versus build: Point\/counterpoint\n\n\n\nOn the other side of the balance sheet, determining a \"return on investment\" for any software implementation is very difficult because the software typically does not generate new income but rather improves the operational efficiency of the entire clinical service. Even if one could objectively measure staff efficiency, productivity, or frustration levels, there are many other variables that contribute those practice characteristics. However, the greatest benefits to staff efficiency are obtained when there is a very high compatibility between the software and your \"ideal\" workflow. For third-party solutions, how good is the fit between what the software was designed to do and what you need it to do? For solutions developed in collaboration with your LIS vendor, how well can you articulate your needs in the form of specifications? The primary advantage of custom software development is that it is likely to result in the greatest efficiency improvements because it can be specifically tailored for your unique environment, which may include consideration of issues such as preferred and supported platforms, level of IT support available, other institutional systems and policies, idiosyncrasies of the users, and specific elements of the workflow. Additionally, unlike most commercially acquired software, software developed in-house can be adapted and modified as the needs become better defined through use and\/or change over time. In other words, your custom solution will become an up-to-date reflection of your operational strategy. You will also likely find that once a solution to a problem has been developed and deployed, other related problems can be addressed by adding incremental functionality to that solution. For example, in our environment, we discovered that our in-house developed solution for digital image file management could be extended to semi-automate the management of scanned documents. This answers the question about what your developers are going to do once they have developed the solution you hired them to develop.\nOne of the most common arguments against software development is the feeling that it requires too many people to do it right. This is not true. Significant improvements in workflow can be obtained with even just one person. Ultimately, it is an issue of scope and time - how large is the project and how quickly does it need to be done? Remember that very little even custom software is written from scratch any more. There are a variety of software frameworks, libraries, and other components available, many for free, some for a small fee, which perform a wide variety of tasks, and most of what the software developer is doing is building a wrapper around these components which ties them together into an integrated system which meshes with the workflow in the department. Software development is not so much about finding enough people but rather about finding the right people with complementary skills that interact in a synergistic fashion. While it is true that having a large number of developers increases the chances that some of them will be the right people, in the end you only really need the right ones. Finding the right people, however, is not easy. Several studies have shown that the individual productivity of software developers with comparable levels of experience can vary by a factor of 10.[9] Many individuals who market themselves as \"programmers\" are really more super-users than programmers. Be sure to require any applicants to submit examples of things they have written, and do a quick web-check to be sure it is not simply something they downloaded from someone else. Ultimately, however, their performance in your environment and in the pathology domain will be the key determinant, but it often takes longer than the standard probationary period to determine whether or not a particular person is right for the team. Over the years, our team has had five other individuals who were either full-time or part-time \"programmers\" before settling on the current team of three. Shortcoming of those no longer on the team included lack of problem-solving skills, poor attention to detail, and in more than one case simply an inability to understand and adapt to the clinical workflow of an academic pathology department.\nMany laboratories will claim that they do not engage in custom software development because they are \"not in the business of writing software.\" However, every high-end clinical laboratory, especially those at \"cutting edge\" academic medical centers, explores new testing technology when it becomes available. When what is commercially available lags behind new scientific developments, many of these labs will either collaborate with vendors to develop the needed technology or develop and validate it themselves as a \"laboratory-developed test.\" This is because pathology laboratories are in the business of technology adoption and development in order to make the most modern diagnostic testing available to enhance patient care. Software is simply another technology - a part of the laboratory's strategy to provide better clinical services - and as such falls well within the scope of \"the business\" of laboratories.\nFinally, one of the most common arguments made against developing clinical software in-house is the concern over who will support the software if the person who developed it leaves the institution. Clinical labs have a responsibility not only to their financial health but also to the patients on whose specimens they perform testing, and the clinicians who care for those patients. To assure longer term stability, most healthcare IT directors prefer to restrict the source of software for clinical purposes to large commercial vendors who have been around for years and are likely to continue to be around for additional years. Smaller third-party vendors offering acceptable solutions raise concern about the company's stability, especially in the current environment of numerous technology company failures. Custom software development is often discouraged. In fact, for a number of years after the creation of the informatics unit at our institution, we resisted going down the path of custom software development precisely to preserve external supportability. However, after many years of struggling with workflow inefficiencies caused by insufficient software, we ultimately decided that even if we only got a few years of use out of a custom solution, the efficiency gains during those few years would be sufficient to justify the development costs. Our vulnerability to the possible unexpected departure of a custom solution developer has been lessened by the extensive use of open-source software (OSS) (see discussion below) and by developing our software using a team approach, as it is unlikely that the entire team would leave simultaneously. In reality, even if a key developer were to leave, the existing software does not stop functioning. If it does, that would suggest it required constant maintenance, and then it was probably too expensive to maintain anyway. If it is a very valuable piece of software, a \"quick repair\" could be subcontracted to get the solution working again while other or new developers are hired to either support the existing software or redevelop it using newer development tools, likely resulting in a superior end result.\n\nCustom software development process \nThere is no one right way to develop custom software, but there are some standard processes that tend to yield superior results. The step-by-step process is summarized in [Table 2].\n\n\n\n\n\n\n\n\n\n Table 2: Custom software development process\n\n\n\nFunctional specification \nThe most important part of custom software development is preparation of the specifications document(s). These are often divided into functional specs and technical specs, but ideally can be combined into a single document depending on the scope of the project and the breath of knowledge of the individuals involved. If done sequentially, the functional specification has to come first, and is the more important of the two. If the functional specifications are not complete, thorough, and well conceived, a lot of wasted effort and re-engineering will be required later in the development process. The functional specs describe the look and feel of the software to be developed. It requires a clear understanding of what problem the software is supposed to solve, and how the solution will be used in the workflow. It is best if this document is prepared by a pathologist rather than by an \"IT\" person. It should not be a \"high-level\" document, but rather should be very specific, ideally down to diagrams of the screens and a description of what should happen when the user interacts with each control (button, checkbox, drop-down list, etc.) on the screen. End-users may not be able to conceptualize the application at this level. Rather, they will provide \"use-cases\", descriptions of when they would use the software and what they need it to do. The author of the functional specification then needs to take these use-cases into account, assimilate the information, and design an application that meets user's needs. The design should take into account where the software will be used (screen size, processor and memory requirements, space for other resources such as keyboard, mouse, and scanners). Finally, appropriate consideration needs to be given to whom the primary users are going to be, and that includes their likely skill set and personalities. What are the users willing to do? For example, if the designed software requires too many mouse clicks, too much typing, or has delays that routinely exceed half a second, many pathologists will be very resistant to adoption, and the solution may fail simply because users avoid using it. It is very useful if multiple potential users can review and have input on the functional specification, both to help assure the solution is general enough to be usable across multiple subspecialties (if appropriate) and to obtain greater buy-in from the user base.\n\nTechnical specification \nWhen the functional specs are completed, the document can be handed-off to IT staff to develop the technical specification. Depending upon the scope of the project, multiple technical individuals with different areas of expertise may be appropriate (e.g., application developer and database designer). During this phase, the data structures will be developed and the overall architecture of the application will be designed. The most appropriate application delivery method (e.g., desktop application, client-server, web application) needs to be determined since this will affect the structure of the application. Typically, splitting the solution into modules is desirable, especially if the modules are independent enough that they can be developed and deployed gradually. The technical design phase also has to take into account the scalability of the application. How many total and\/or simultaneous users will there be? How much data will the application accumulate? These issues have implications for database table structure, indexing, memory requirements, etc. Finally, it might be a good idea, even at this phase, to consider the maintenance needs of the application. How much ongoing maintenance will be needed, and who will do it? For example, a solution that automatically files a high volume of material but requires manual intervention to process failed filing events will need ongoing resources for the manual processing.\nIn our environment, the majority of the specifications are combined, functional and technical, and are prepared by a pathologist with informatics experience. Specification documents can vary in length significantly based on the scope of the application, and ours have ranged from about five pages to over 100. The specification document(s), particularly the technical components, should be considered a dynamic document, and may have to be modified as the application is developed to fine-tune the final product.\n\nSoftware development \nThe actual software writing is the most variable part of the development process. Individual programmers will have different skills, and different preferences for development platforms (operating system as well as integrated development environments) and programming languages. The use and integration of open-source frameworks and components can substantially facilitate this process, as well as mitigate many of the risks often associated with custom software development. OSS is software developed by self-selected groups of programmers and made available to the public for use, modification, and incorporation into their own solutions. Many OSS projects have some management infrastructure and follow formal process (e.g., Free Software Foundation, Apache Foundation, Mozilla Foundation, etc.). Typically, this software is available for free, but may carry some restrictions about future commercialization, which is usually not a problem for pathology departments developing custom solutions to problems because there is no intention to subsequently commercialize the product. There are thousands of OSS projects available for download at GNU Savannah (savannah.gnu.org), sourceforge.net, Google code, etc. Well-written solutions are very popular, and as such are extremely well tested and debugged by multiple users, and updates with new features and some bug fixes are routinely produced. OSS can include fully operational solutions (e.g., Linux operating system, MySQL database, Apache Web Server, Apache Tomcat), development tools (e.g., Eclipse integrated development environment, Google Web Toolkit), as well as frameworks (Sprint, Hybernate, Quartz, etc.), component libraries and application programming interfaces (e.g., HAPI application programming interface, iText, jFreeChart, Apache Commons) that can be integrated into custom software such as HL7 engines, PDF generation, scheduling engines, and charting\/graphing solutions. Use of open-source components substantially mitigates the risks of custom software development because it markedly reduces the volume of code to be written, expedites development, and minimizes bugs and errors because significant portions of the solution have already been tested by a large number of users. You retain the ability to modify the software to meet your current or future needs.\nThere is substantial literature on Rapid Application Development, and various methodologies have been used to improve productivity and deliver working code to the end-user in the shortest amount of time, maintaining a balance between development time and the quality of the end product. The essence of these approaches is outlined in the Agile Software Development Manifesto.[10][11] It was critical for us to adopt these Agile Principles in our development process because the speed of implementation of new functionality is one of the key benefits of in-house code development. Open source, with its philosophy of \"release early, release often,\" feeds well into this methodology.[12] This philosophy is typically well received in medical environments because users can see ongoing improvements and more importantly can provide feedback and input which may alter the direction of the project toward a superior final product.\nFinally, developing custom software for clinical use obviously requires a \"test environment.\" The clinical mission of the department must go on, and cannot be compromised by the occasional runaway process and\/or system crash that invariably occurs during software development. As much as possible, the test environment should mimic the production environment.\n\nValidation \nCustom software for clinical use should be treated like any other laboratory-developed test and appropriately validated before it is used in a clinical setting. Validation (not to be confused with autovalidation of test results) may be governed by regulatory statutes, and those need to be considered carefully (Note that while we hope the discussion here proves helpful, it should not in any way be considered a comprehensive evaluation of the current legal and regulatory environment surrounding software development for clinical use). The Food and Drug Administration (FDA) of the United States Federal Government has oversight responsibility and authority for \"medical devices.\" Software integrated into medical devices has always, therefore, been regulated by the FDA. The FDA does consider LISs in general to be medical devices, but these have been exempt from the 510(k) approval process since June of 1988.[13] In contrast, because of its charge to regulate blood products, the FDA in March of 1994 determined that any software used in healthcare \"for the maintenance of data that personnel use in making decisions regarding the suitability of donors and the release of blood or blood components for transfusion\" is required to undergo the 510(k) approval process.[14] Given this requirement, development of any custom software that touches on blood product management should be approached cautiously. It is worth noting that in 2011, the FDA issued a new regulation pertaining to what they define as \"Medical Device Data Systems\" (MDDSs).[15] This includes standalone software which stores and\/or displays data derived from medical devices. This new regulation reclassifies MDDSs from Class III devices to Class I devices, substantially softening the regulatory requirements for bringing these systems to market. Developers of such software, including healthcare facilities, are required to register and list with the FDA. With respect to custom software development for in-house use only, however, the Code of Federal Regulation which governs the operation of the FDA specifically defines as \"exempt from registration\" any \"licensed practitioners, including physicians, dentists, and optometrists, who manufacture or otherwise alter devices solely for use in their practice\" (21 CFR 807.65(d)).[16] Thus, there does not appear to be any current requirement to notify the FDA if you are developing software for use within your own institution, but this does not exempt the developers from validating their software. Moreover, as laboratorians, pathologists recognize the value and need for good quality control practices in the generation and distribution of any data used for patient care. The FDA does provide some useful guidance in this regard. In their Laboratory Manual of Quality Policies under Test Methods and Validation, they state \"5.4.7.2 Computer Use: When computers or automated equipment are used for the acquisition, processing, recording, reporting, storage or retrieval of test data, if computer software is developed by the user, its development is documented in detail and algorithms are validated.\"[17] Additionally, in 2002, the FDA released a guidance document entitled \"General Principles of Software Validation.\"[18] This document defines software validation as: \"Confirmation by examination and provision of objective evidence that software specifications conform to user needs and intended uses, and that the particular requirements implemented through software can be consistently fulfilled (Section 3.1.2).\" The guidance document acknowledges that determining how much testing is \"enough\" is difficult and that a developer \"cannot test forever.\" Rather, the goal is to achieve a \"level of confidence that the [software] meets all requirements and user expectations.\"\nFrom a very practical standpoint, the extent of the validation needed depends on what the software does. Does it create new data, or does it simply display data already captured\/created from other validated systems in a new way? Will it be immediately obvious to the user if the software is not functioning properly, or is there a risk that using the software could result in an inappropriate clinical action? The greater the risk, the more extensive the validation activities need to be. For low-risk solutions, end-users can be part of the validation process via pilot phases. Users typically will not \"accept\" software that does not do what it is supposed to do, especially if they know that that software was developed in-house and thus could be fixed. Finally, an important part of the validation process is documentation. This includes the initial design specifications, documentation within the code itself, documentation of testing, and detailed instructions of what changes are needed to the production environment for deployment.\n\nSolution deployment \nDeployment strategies for custom software can vary significantly and are dependent upon the scope of the solution developed. Is the code a standalone solution, an integrated solution, or are there components of both? What kind of concurrency is required between the two? For example, if you have engineered a composite solution with some standalone software and some software integrated into your LIS, can the standalone component exist without the presence of the LIS integrated component, or do they both have to be deployed simultaneously? Once deployed, is use of the software optional (e.g., an alternate way of doing something) or is it integral (it now becomes the only way to do something)? Either way, the code ultimately needs to be transferred to and set up in the production environment, and this is a great opportunity to double-check the documentation you have developed to make sure it is complete. The documentation should include all the components of the solution and any changes needed in the production environment for the software to operate properly.\nIf the software can be kept somewhat isolated (i.e., its use is not required in the workflow), a pilot phase is strongly recommended. In this phase of the process, a select group of users is chosen to try out the software for some or all of their cases for a period of time. Whenever possible, this should include those pathologists involved in the functional design of the software. Important feedback can be obtained from using the software \"for real,\" and this may result in some modifications or update to improve the synergy with the workflow.\nIf the software cannot be kept isolated (i.e. its use, upon deployment, becomes required), then a back-out strategy needs to be developed in advance. What will you do if the software does not work as expected? It is usually not feasible to simply stop all work in the department while it is being fixed. There are times when deployment has no practical back-out strategy (such as upgrading the LIS to a new version), and in such instances it is typically prudent to perform the deployment on a weekend when there is less time pressure associated with returning the system to a fully operational status.\nFor large development projects with multiple modules, one may have to choose between deploying modules individually or all at once. A staged deployment is often preferable, since users seem to respond better to smaller, incremental changes than to complete workflow changes. One may also have to decide between applying a workflow change to a subset of the specimens initially, or to all of the specimens at the same time. While the former may seem to carry less risk, remember that you are then creating two different workflows (the new and the old) which are operating side-by-side in the same lab, and that can be more disruptive than applying the change to all specimens from the start.\nUser training is always advisable in advance of any deployment, although this can be harder to accomplish in practice than in theory. Users do not typically have a lot of spare time in their workday, and there can be little incentive to learning something new that is not immediately applicable. We have found it more effective to simply inform everyone well in advance (about a week), give the new users an overview of what the new workflow will look like, perhaps allow them to choose when would be the best day\/time for the deployment, and then provide significant on-site support at the time of the roll-out, with the developers and ideally the pilot users and functional designers present\/available to help answer questions (which often take the form of \"why do I have to do it this way?\" rather than \"what am I supposed to do next?\").\nCareful monitoring of the performance of the new software is needed following deployment. Despite extensive testing, there is no way to adequately anticipate the variety of ways users will find to use the new software, and this may uncover subtle deficiencies in either the design or the development which have to be addressed. Remember that many users are pretty clever and may find ways around using the software as intended, especially if it sometimes does not work quite right. Users may identify problems, but simply work around them rather than notifying anyone. We have found it useful to remind users about a week after deployment that the development team needs to be informed of any unusual behavior or possible bugs. It is not an infrequent occurrence at our institution where, for example, a pathologist involved in the development notices weeks later when they are on service an issue with the software which, when queried, everyone acknowledges having noticed but no one made any attempt to notify the development team about.\n\nUpdates and enhancements \nInvariably, small bugs will be identified in any custom software which need to be addressed, but the frequency of detection does drop-off quickly after the software has been used for a couple of weeks. Sometimes, developing and deploying what is thought to be the ideal solution provide a better understanding of the problem, and that better understanding may suggest modifications to the software to create a superior solution. More commonly, an onslaught of suggestions for additional improvement will arise, and this should be interpreted as a sign of great success. Having seen what it is possible to accomplish with custom software and the workflow improvements that can result, users are inspired to think of additional improvements that will provide even greater benefits. It is important to have a process for aggregating these suggestions, appropriately vetting them with the design team. Is this a general improvement, or something that satisfies the idiosyncrasies of an individual user? Does it move the solution in the desired direction, or backward closer to the original workflow? Is it a small change or a large one that will require substantial re-engineering? It is often valuable to allow the deployed software to incubate with users for a while before rapidly responding to requests for changes. However, once the developed software has stabilized in the workflow, new opportunities for even greater workflow enhancement can be explored. Once a solution has been developed, incremental additions can progressively expand the scope of the solution to solve additional, related problems. This flexibility and the capability to respond quickly as needs become better-understood or change, or as additional needs arise, without having to embark on a new series of vendor negotiations is one of the true values of custom software development.\nFrom the developer perspective, there are two relatively common pitfalls to be avoided, and these depend on the personalities of the programmers. The first is to abandon ownership of the application too early. Developers tend to like to develop, not support. But support groups within the department or institution will not understand the new application. They will not know what it is supposed to do, and what it can do. Integral involvement of at least a portion of the development team with the initial users can be critical to proper use and acceptance of the new software. Additionally, if any unanticipated behavior of the new solution is uncovered, it is an opportunity for the developers to see that first hand within the real-life use of the application. The second pitfall which developers can fall into is to never abandon their application. Developers can become attached to the product of their efforts, and may take to repeated reworking and refactoring of their solution to make it a little better. Perhaps a little redesign of a particular routine will make it run a little faster, or make it a little more generalizable. These activities, which typically affect the \"back-end\" of the application but have no visible effect to the users or the functionality, need to be examined critically with respect to what value they are truly providing. Avoid the trap of updating the application each time a new version of a library or other tool becomes available because this can consume significant resources with minimal yield. Even after a number of years, some developers may wish to cling to their initial code beyond its practical viability. Five or so years after the initial writing, it may be faster, cheaper, and more reliable to rewrite the solution from scratch using new tools rather than trying to update prior code. The logic for the solution has already been developed and worked out and usually can be transferred directly to a new development environment with minimal modifications.\n\nProject leadership \nOne aspect of software development that has been absent from this discussion is that of project leadership. This is largely because the software development team in our Pathology Informatics Unit is rather small (essentially three people) and the decision-making hierarchy is clear. For larger groups, however, it is important to have a single individual ultimately responsible for the application. This individual should approve any changes to the specifications during the development process. They need to understand all facets of the solution and the workflow in which it will be used, and have the clarity of thought to be able to anticipate the implications for how modifications to one part of the application will affect other parts.\n\nConclusion \nDespite commonly voiced and exaggerated concerns over the costs and risks associated with custom software development, tremendous yields in productivity and efficiency can be achieved with relatively modest investments. Both the costs and the risks can be mitigated by incorporating OSS into the solution, and by having a well-structured development process. Having the right people involved is far more important than the number of people, and involvement of individuals with a deep knowledge of the workflows which may be affected is crucial to the success of the development process. Ultimately, software is a tool. That tool needs to fit your needs, your environment, and your workflow. That tool needs to be adaptable in a time frame consistent with the changing practice of clinical laboratories, and has to strategically advance the mission of the lab to provide the highest quality patient care. The focus should be not on how the tool comes into existence, but on the benefits obtained from its use. When commercially available solutions fall short of the needs, custom software development is a viable, often superior solution.\n\nSource of support \nNone\n\nConflict of interest \nNone\n\nReferences \n\n\n\u2191 Sinard, J.H.; Mattie, M.E. (2005). \"Overcoming the limitations of integrated clinical digital imaging solutions\". Archives of Pathology & Laboratory Medicine 129 (9): 1118-26. doi:10.1043\/1543-2165(2005)129[1118:OTLOIC]2.0.CO;2. PMID 16119983.   \n\n\u2191 Sinard, J.H.; Gershkovich, P. (2009). \"Semiautomated Archiving of Scanned Requisition Documents in Anatomic Pathology - Advancing Practice, Instruction, and Innovation Through Informatics (APIII 2008) Conference\". Archives of Pathology & Laboratory Medicine 133 (7): 1148-1165. doi:10.1043\/1543-2165-133.7.1148. http:\/\/www.archivesofpathology.org\/doi\/full\/10.1043\/1543-2165-133.7.1148 .   \n\n\u2191 Sinard, J.H.; Gershkovich, P. (2010). \"Integrating Digital Dictation and the Anatomic Pathology Laboratory Information System - Advancing Practice, Instruction, and Innovation Through Informatics (APIII 2009) Conference\". Archives of Pathology & Laboratory Medicine 134 (6): 936-948. doi:10.1043\/1543-2165-134.6.936. http:\/\/www.archivesofpathology.org\/doi\/10.1043\/1543-2165-134.6.936 .   \n\n\u2191 Sinard, J.H.; Gershkovich, P. (2009). \"Use of a Repetitive Task Scheduling Engine for Workflow Automation and Rare Event Detection in a Clinical Environment - Advancing Practice, Instruction, and Innovation Through Informatics (APIII 2008) Conference\". Archives of Pathology & Laboratory Medicine 133 (7): 1148-1165. doi:10.1043\/1543-2165-133.7.1148. http:\/\/www.archivesofpathology.org\/doi\/full\/10.1043\/1543-2165-133.7.1148 .   \n\n\u2191 5.0 5.1 Gershkovich, P.; Mutnick, N.; Sinard, J.H. (September 2010). \"FSLink-Frozen Section Management Software with Real-Time Communication with the OR\". Association for Pathology Informatics, 2010 Annual Meeting, Boston, MA. Association for Pathology Informatics. http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule .   \n\n\u2191 Sinard, J.H.; Mutnick, N.; Gershkovich, P. (September 2010). \"Histology Asset Tracking: Hidden Practices and Their Consequences\". Association for Pathology Informatics, 2010 Annual Meeting, Boston, MA. Association for Pathology Informatics. http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule .   \n\n\u2191 Sinard, J.H.; Mutnick, N.; Gershkovich, P. (September 2010). \"Histology Asset Tracking Dashboard: Real-Time Monitoring and Dynamic Work Lists\". Association for Pathology Informatics, 2010 Annual Meeting, Boston, MA. Association for Pathology Informatics. http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule .   \n\n\u2191 Sinard, J.H.; Mutnick, N.; Gershkovich, P. (2011). \"Facilitating Feedback and Education on the Hot Seat Rotation - Abstracts: Pathology Informatics 2011 Meeting\". Journal of Pathology Informatics 2: 43. PMC PMC3238568. http:\/\/www.jpathinformatics.org\/text.asp?2011\/2\/1\/43\/85679 .   \n\n\u2191 Mills, H.J. (1983). Software Productivity. Little, Brown. pp. 274. ISBN 9780316573887. https:\/\/books.google.com\/books\/about\/Software_Productivity.html?id=-JdQAAAAMAAJ .   \n\n\u2191 Beck, K.; Bennekum, A.; Cockburn, A. et al. (2001). \"Manifesto for Agile Software Development\". Ward Cunningham. http:\/\/www.agilemanifesto.org\/ . Retrieved 01 September 2012 .   \n\n\u2191 Beck, K. (2003). Test-Driven Development by Example. Addison-Wesley Professional. ISBN 9780321146533. https:\/\/books.google.com\/books\/about\/Test_driven_Development.html?id=gFgnde_vwMAC .   \n\n\u2191 Raymond, E.S. (02 August 2002). \"The Cathedral and the Bazaar\". Thyrsus Enterprises. http:\/\/www.catb.org\/~esr\/writings\/cathedral-bazaar\/cathedral-bazaar\/index.html . Retrieved 18 August 2012 .   \n\n\u2191 US Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health (09 September 1999). \"Guidance for Industry, FDA Reviewers and Compliance on Off-The-Shelf Software Use in Medical Devices\". Food and Drug Administration. pp. 16. Archived from the original on 01 September 2012. https:\/\/web.archive.org\/web\/20110901191855\/http:\/\/www.fda.gov\/MedicalDevices\/DeviceRegulationandGuidance\/GuidanceDocuments\/ucm073778.htm . Retrieved 01 September 2012 .   \n\n\u2191 US Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (31 March 1994). Blood Vaccines\/Guidance Compliance Regulatory Information\/Other Recommendations for Manufacturers\/Memorandum to Blood Establishments\/UCM062804.pdf \"Software Used in Blood Establishments\" (PDF). Food and Drug Administration. pp. 3. http:\/\/www.fda.gov\/downloads\/Biologics Blood Vaccines\/Guidance Compliance Regulatory Information\/Other Recommendations for Manufacturers\/Memorandum to Blood Establishments\/UCM062804.pdf . Retrieved 18 August 2012 .   \n\n\u2191 US Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health (15 February 2011). \"MDDS Rule\". Food and Drug Administration. http:\/\/www.fda.gov\/MedicalDevices\/ProductsandMedicalProcedures\/GeneralHospitalDevicesandSupplies\/MedicalDeviceDataSystems\/ucm251897.htm . Retrieved 18 August 2012 .   \n\n\u2191 \"United States Code of Federal Regulations, Title 21, Part 807, Section 65\". Food and Drug Administration. http:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?fr=807.65 . Retrieved 01 September 2012 .   \n\n\u2191 US Department of Health and Human Services, Food and Drug Administration, Office of Regulatory Affairs, Division of Field Science (2012). \"Vol. I. Section 5.4.7.2: Laboratory Manual of Quality Policies for ORA Regulatory Laboratories\". Food and Drug Administration. p. 33. http:\/\/www.fda.gov\/ScienceResearch\/FieldScience\/LaboratoryManual\/ . Retrieved 01 September 2012 .   \n\n\u2191 US Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health (2012). \"General Principles of Software Validation; Final Guidance for Industry and FDA Staff\". Food and Drug Administration. p. 6. http:\/\/www.fda.gov\/MedicalDevices\/DeviceRegulationandGuidance\/GuidanceDocuments\/ucm085281.htm . Retrieved 01 September 2012 .   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Custom_software_development_for_use_in_a_clinical_laboratory\">https:\/\/www.limswiki.org\/index.php\/Journal:Custom_software_development_for_use_in_a_clinical_laboratory<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on software\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 23 March 2016, at 19:43.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 1,090 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","54f8c03773fbcda29fa23c857f6a1159_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_Custom_software_development_for_use_in_a_clinical_laboratory skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Custom software development for use in a clinical laboratory<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>In-house software development for use in a <a href=\"https:\/\/www.limswiki.org\/index.php\/Clinical_laboratory\" title=\"Clinical laboratory\" target=\"_blank\" class=\"wiki-link\" data-key=\"307bcdf1bdbcd1bb167cee435b7a5463\">clinical laboratory<\/a> is a controversial issue. Many of the objections raised are based on outdated software development practices, an exaggeration of the risks involved, and an underestimation of the benefits that can be realized. Buy versus build analyses typically do not consider total costs of ownership, and unfortunately decisions are often made by people who are not directly affected by the workflow obstacles or benefits that result from those decisions. We have been developing custom software for clinical use for over a decade, and this article presents our perspective on this practice. A complete analysis of the decision to develop or purchase must ultimately examine how the end result will mesh with the departmental workflow, and custom-developed solutions typically can have the greater positive impact on efficiency and productivity, substantially altering the decision balance sheet. Involving the end-users in preparation of the functional specifications is crucial to the success of the process. A large development team is not needed, and even a single programmer can develop significant solutions. Many of the risks associated with custom development can be mitigated by a well-structured development process, use of open-source tools, and embracing an agile development philosophy. In-house solutions have the significant advantage of being adaptable to changing departmental needs, contributing to efficient and higher quality patient care.\n<\/p><p><b>Keywords<\/b>: Buy versus build, clinical use, custom software, in-house development, open source\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Facing_unmet_needs\">Facing unmet needs<\/span><\/h3>\n<p>Computer software is an integral part of the day-to-day operation of any clinical laboratory. The major nidus for this activity is the <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_system\" title=\"Laboratory information system\" target=\"_blank\" class=\"wiki-link\" data-key=\"37add65b4d1c678b382a7d4817a9cf64\">laboratory information system<\/a> (LIS), typically a suite of integrated modules purchased from a single vendor and designed specifically for the operation of the <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" target=\"_blank\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratory<\/a>. LISs have matured substantially over the past few decades, providing greater operational efficiency and improving patient safety.\n<\/p><p>Yet, even the most advanced LISs do not fully meet the needs of every laboratory. Although some labs may be able to function adequately on their LIS, larger labs and labs providing specialty services typically can identify information management needs which are not met by their LIS. This is because <a href=\"https:\/\/www.limswiki.org\/index.php\/LIS_vendor\" title=\"LIS vendor\" target=\"_blank\" class=\"wiki-link\" data-key=\"28459eb218e1163e19c62c819c9c4b34\">LIS vendors<\/a> build their software to meet the needs common to the majority of the labs in their current or intended client base rather than to meet the needs of a particular lab, and every lab has some unique needs due to their size, subtleties of their local environment, people, and the clinical focus of their clients. Thus, a needed functionality is lacking, either because it does not exist at all in the LIS, or because it exists in a way that does not mesh well with the workflow in the lab.\n<\/p><p>When the LIS functionality falls short of an identified need, labs have a choice: (1) make do with what they have, perhaps adjusting their workflow to accommodate; (2) contract with the LIS vendor to add the needed functionality to their LIS, or to modify it to meet their workflow needs; (3) purchase third-party software which meets the need, (4) develop their own custom software in-house, or (5) purchase a new LIS. Purchasing a new LIS is a huge undertaking and outside of the scope of this discussion. In fact, most labs choose to go with option 1. There can be many ways to accomplish a task in the lab, and labs can adapt to what their LIS is able to do. If the need is great and funds can be identified, option 2 may be chosen. Having your LIS vendor develop integrated customizations assures compatibility with the rest of the LIS, but this can be an expensive and time-consuming process. Nonetheless, LIS vendors rely on at least some clients choosing this option because this funds enhancements to their product. When laboratory science or the regulatory environment creates a general need, the client with the lowest threshold, greatest need, and available capital funds the development of the solution with their vendor. This client has the advantage of dictating how the workflow for the new feature will be designed. After delivery and testing (and payment), the vendor typically incorporates the new feature into a subsequent version of the LIS software, either as a free enhancement or available for an additional charge.\n<\/p><p>Third-party solutions can be a good option, and certainly should be investigated. If your lab has an unmet need, others probably have a similar need. There are a number of smaller companies that are more nimble than the major LIS vendors and that can respond more quickly to a need and provide a solution. The less specific the need is to <a href=\"https:\/\/www.limswiki.org\/index.php\/Clinical_pathology\" title=\"Clinical pathology\" target=\"_blank\" class=\"wiki-link\" data-key=\"9b0b91aa13ae0209e073db6f30493daf\">pathology<\/a> (e.g., transcription, image acquisition), the more likely it is that there will be multiple solutions from which to choose. If the solution can operate independent of the LIS, there are no integration concerns. If it needs to be integrated, the company may be able to handle it themselves, unless modifications are needed to the LIS system, in which case the third-party company will then likely have to enter into some sort of agreement with the LIS vendor. There are many examples of successful third-party solutions, the most common of which is \"middleware\" in the clinical laboratories, which manages communication between analytical instruments and the LIS.\n<\/p><p>However, if the need is novel or specific for your environment, third-party products that adequately meet that need are often simply not available. In this situation, in-house custom software development may be the best solution.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Our_experience\">Our experience<\/span><\/h2>\n<p>At our institution, the pathology department provides <a href=\"https:\/\/www.limswiki.org\/index.php\/Anatomical_pathology\" title=\"Anatomical pathology\" target=\"_blank\" class=\"wiki-link\" data-key=\"5668db6faf37e8c1432a1d7953f30cb7\">anatomic pathology<\/a> services only (laboratory medicine is a separate department). We have our own <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_informatics#Clinical_informatics\" title=\"Health informatics\" target=\"_blank\" class=\"wiki-link\" data-key=\"cb1d520aeb5af387d6835ac6cf8d1cc7\">Pathology Informatics<\/a> Unit that provides both operational services (i.e., information technology services) and software development. We also have three other full-time faculty members with academic <a href=\"https:\/\/www.limswiki.org\/index.php\/Informatics\" title=\"Informatics\" class=\"mw-disambig wiki-link\" target=\"_blank\" data-key=\"ea0ff624ac3a644c35d2b51d39047bdf\">informatics<\/a> programs, but they are not involved in the software development for clinical use. Our clinical development team has developed a variety of clinical applications that are used every day in our anatomic pathology practice. Some of these solutions are integrated into and\/or interact with our LIS, and some are standalone solutions. Our development team consists of three people. One is a pathologist, who also has other significant clinical and administrative needs and thus spends only about 20% of his time on software development. His primary role is in specification development and in programming the department's LIS to interact with the custom software (we have a unique arrangement without LIS vendor which allows us to introduce our own customizations into the commercial software, which was nicely designed to allow for this process). Another developer handles the user interface creation (according to the provided specifications) and also handles deployment, user training, and initial support of the custom applications. The third developer spends approximately two-thirds of his time on development, predominantly the business logic of the standalone components of the application, with the other third spent on management of the operational informatics unit in the department. Thus, in total, this represents about 1.6 FTEs (full-time equivalents) of true development resources. Our LIS is <a href=\"https:\/\/www.limswiki.org\/index.php\/Cerner_Corporation\" title=\"Cerner Corporation\" target=\"_blank\" class=\"wiki-link\" data-key=\"44b952d5fb439af88c84f5ad453fee3f\">Cerner<\/a> CoPathPlus. Our standalone components are developed in Java, predominantly as web applications.\n<\/p><p>Over the past several years, solutions we have developed and deployed include: Digital image file management<sup id=\"rdp-ebb-cite_ref-SinardOver05_1-0\" class=\"reference\"><a href=\"#cite_note-SinardOver05-1\" rel=\"external_link\">[1]<\/a><\/sup>, scanned document file management<sup id=\"rdp-ebb-cite_ref-SinardSemi09_2-0\" class=\"reference\"><a href=\"#cite_note-SinardSemi09-2\" rel=\"external_link\">[2]<\/a><\/sup>, dictation\/transcription management<sup id=\"rdp-ebb-cite_ref-SinardInt10_3-0\" class=\"reference\"><a href=\"#cite_note-SinardInt10-3\" rel=\"external_link\">[3]<\/a><\/sup>, an outreach support system for orders and report delivery, an outreach client interface system, a repetitive task scheduling engine<sup id=\"rdp-ebb-cite_ref-SinardUse09_4-0\" class=\"reference\"><a href=\"#cite_note-SinardUse09-4\" rel=\"external_link\">[4]<\/a><\/sup>, frozen section management and diagnosis communication to operating rooms<sup id=\"rdp-ebb-cite_ref-GeshkovichFSLink10_5-0\" class=\"reference\"><a href=\"#cite_note-GeshkovichFSLink10-5\" rel=\"external_link\">[5]<\/a><\/sup>, histology asset tracking<sup id=\"rdp-ebb-cite_ref-SinardHATHid10_6-0\" class=\"reference\"><a href=\"#cite_note-SinardHATHid10-6\" rel=\"external_link\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-SinardHATDash10_7-0\" class=\"reference\"><a href=\"#cite_note-SinardHATDash10-7\" rel=\"external_link\">[7]<\/a><\/sup>, trainee diagnosis tracking and evaluation<sup id=\"rdp-ebb-cite_ref-SinardFac11_8-0\" class=\"reference\"><a href=\"#cite_note-SinardFac11-8\" rel=\"external_link\">[8]<\/a><\/sup>, and numerous databases to support trainee interviewing and recruitment, graduate trainee tracking, computer hardware tracking, research histology, and graphics services billing. This article is based on our collective experience with this development and deployment process.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Buy_versus_build\">Buy versus build<\/span><\/h2>\n<p>Medical institutions operate around a number of philosophies, some codified in actual policies, but most driven by the experiences and\/or preferences of the institutional leadership. In the information technology (IT) departments, one of the most prevalent dichotomies is the preference to buy or build: When an unmet IT need arises, does one buy a commercially available solution or invest in building\/developing a custom solution? Although there is a lot of software commercially available, it is generally not designed for some of the specialty medical uses and may not mesh well with the existing workflow. In many environments, the task of assessing the suitability of available software to meet a specific need is often relegated to IT staff who are not that familiar with the clinical workflow. A solution is purchased and installed which does not fit quite right. Since the \"off-the-shelf\" software is generally not modifiable by the end-user, departments then find themselves adjusting their workflow to match what the software can do. Advocates for the \"build\" philosophy argue that computers are a tool that should be adapted to the user's workflow rather than dictating a particular workflow to its users.\n<\/p><p>Advocates for the \"buy\" philosophy raise a number of common objections to development of software in-house. These, along with counter arguments, are listed in [Table 1]. In addressing any unmet software need, it is always prudent to explore what solutions might be commercially available, either through your LIS vendor or from a third-party. There is a lot of software available commercially from a large number of vendors. How \"thorough\" of an investigation one does depends, of course, on the need and potential benefits, since exploring options can be time-consuming. If your need is unique, however, there may simply be nothing available which comes close. We experienced that when we developed the specifications for our Frozen Section Management and Diagnosis Communication software.<sup id=\"rdp-ebb-cite_ref-GeshkovichFSLink10_5-1\" class=\"reference\"><a href=\"#cite_note-GeshkovichFSLink10-5\" rel=\"external_link\">[5]<\/a><\/sup> The buy versus build cost\/benefit analysis needs to consider the true cost of ownership, not simply the difference between the purchase cost and the development cost. On the buy side, one must include the costs of installing and setting up the new software, included in the cost of most large vendor offerings, but sometimes an additional charge from smaller vendors. Are there additional hardware costs associated with the new software, like workstation upgrades? Are there expenses associated with integrating the new software into your workflow, including any workflow changes and perhaps personnel changes? Does the solution require purchasing specific consumables such as a particular vendor's labels, cassettes, or slides? There may also be subsequent annual support costs, which often run 22-25% of the initial purchase price. Collaborating with your LIS vendor to develop the solution as part of the LIS is an option, but can be expensive, and there will almost certainly be annual support cost increases. Additionally, the vendor will be limited by the technology used to develop the LIS, often technology that is a decade old. Determining the cost of developing software in-house can be difficult, but it usually comes down to people and time - the faster you need the software completed, the more people it may take. The more people you hire, the more expensive it is, and then there is the issue of what are you going to do with those people after the software has been developed? (This is discussed further later.)\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Sinard_JPathologyInformatics2012_3.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"686babb56addfe2d6e741a61f3ca63c6\"><img alt=\"Fig1 Sinard JPathologyInformatics2012 3.jpg\" src=\"https:\/\/www.limswiki.org\/images\/5\/5f\/Fig1_Sinard_JPathologyInformatics2012_3.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Table 1: Buy versus build: Point\/counterpoint<\/b><\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>On the other side of the balance sheet, determining a \"return on investment\" for any software implementation is very difficult because the software typically does not generate new income but rather improves the operational efficiency of the entire clinical service. Even if one could objectively measure staff efficiency, productivity, or frustration levels, there are many other variables that contribute those practice characteristics. However, the greatest benefits to staff efficiency are obtained when there is a very high compatibility between the software and your \"ideal\" workflow. For third-party solutions, how good is the fit between what the software was designed to do and what you need it to do? For solutions developed in collaboration with your LIS vendor, how well can you articulate your needs in the form of specifications? The primary advantage of custom software development is that it is likely to result in the greatest efficiency improvements because it can be specifically tailored for your unique environment, which may include consideration of issues such as preferred and supported platforms, level of IT support available, other institutional systems and policies, idiosyncrasies of the users, and specific elements of the workflow. Additionally, unlike most commercially acquired software, software developed in-house can be adapted and modified as the needs become better defined through use and\/or change over time. In other words, your custom solution will become an up-to-date reflection of your operational strategy. You will also likely find that once a solution to a problem has been developed and deployed, other related problems can be addressed by adding incremental functionality to that solution. For example, in our environment, we discovered that our in-house developed solution for digital image file management could be extended to semi-automate the management of scanned documents. This answers the question about what your developers are going to do once they have developed the solution you hired them to develop.\n<\/p><p>One of the most common arguments against software development is the feeling that it requires too many people to do it right. This is not true. Significant improvements in workflow can be obtained with even just one person. Ultimately, it is an issue of scope and time - how large is the project and how quickly does it need to be done? Remember that very little even custom software is written from scratch any more. There are a variety of software frameworks, libraries, and other components available, many for free, some for a small fee, which perform a wide variety of tasks, and most of what the software developer is doing is building a wrapper around these components which ties them together into an integrated system which meshes with the workflow in the department. Software development is not so much about finding enough people but rather about finding the right people with complementary skills that interact in a synergistic fashion. While it is true that having a large number of developers increases the chances that some of them will be the right people, in the end you only really need the right ones. Finding the right people, however, is not easy. Several studies have shown that the individual productivity of software developers with comparable levels of experience can vary by a factor of 10.<sup id=\"rdp-ebb-cite_ref-MillsSoft83_9-0\" class=\"reference\"><a href=\"#cite_note-MillsSoft83-9\" rel=\"external_link\">[9]<\/a><\/sup> Many individuals who market themselves as \"programmers\" are really more super-users than programmers. Be sure to require any applicants to submit examples of things they have written, and do a quick web-check to be sure it is not simply something they downloaded from someone else. Ultimately, however, their performance in your environment and in the pathology domain will be the key determinant, but it often takes longer than the standard probationary period to determine whether or not a particular person is right for the team. Over the years, our team has had five other individuals who were either full-time or part-time \"programmers\" before settling on the current team of three. Shortcoming of those no longer on the team included lack of problem-solving skills, poor attention to detail, and in more than one case simply an inability to understand and adapt to the clinical workflow of an academic pathology department.\n<\/p><p>Many laboratories will claim that they do not engage in custom software development because they are \"not in the business of writing software.\" However, every high-end clinical laboratory, especially those at \"cutting edge\" academic medical centers, explores new testing technology when it becomes available. When what is commercially available lags behind new scientific developments, many of these labs will either collaborate with vendors to develop the needed technology or develop and validate it themselves as a \"laboratory-developed test.\" This is because pathology laboratories are in the business of technology adoption and development in order to make the most modern diagnostic testing available to enhance patient care. Software is simply another technology - a part of the laboratory's strategy to provide better clinical services - and as such falls well within the scope of \"the business\" of laboratories.\n<\/p><p>Finally, one of the most common arguments made against developing clinical software in-house is the concern over who will support the software if the person who developed it leaves the institution. Clinical labs have a responsibility not only to their financial health but also to the patients on whose specimens they perform testing, and the clinicians who care for those patients. To assure longer term stability, most healthcare IT directors prefer to restrict the source of software for clinical purposes to large commercial vendors who have been around for years and are likely to continue to be around for additional years. Smaller third-party vendors offering acceptable solutions raise concern about the company's stability, especially in the current environment of numerous technology company failures. Custom software development is often discouraged. In fact, for a number of years after the creation of the informatics unit at our institution, we resisted going down the path of custom software development precisely to preserve external supportability. However, after many years of struggling with workflow inefficiencies caused by insufficient software, we ultimately decided that even if we only got a few years of use out of a custom solution, the efficiency gains during those few years would be sufficient to justify the development costs. Our vulnerability to the possible unexpected departure of a custom solution developer has been lessened by the extensive use of <a href=\"https:\/\/www.limswiki.org\/index.php\/Category:Open-source_software\" title=\"Category:Open-source software\" target=\"_blank\" class=\"wiki-link\" data-key=\"1aa6da5776c348224e3820317e698a07\">open-source software<\/a> (OSS) (see discussion below) and by developing our software using a team approach, as it is unlikely that the entire team would leave simultaneously. In reality, even if a key developer were to leave, the existing software does not stop functioning. If it does, that would suggest it required constant maintenance, and then it was probably too expensive to maintain anyway. If it is a very valuable piece of software, a \"quick repair\" could be subcontracted to get the solution working again while other or new developers are hired to either support the existing software or redevelop it using newer development tools, likely resulting in a superior end result.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Custom_software_development_process\">Custom software development process<\/span><\/h2>\n<p>There is no one right way to develop custom software, but there are some standard processes that tend to yield superior results. The step-by-step process is summarized in [Table 2].\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Sinard_JPathologyInformatics2012_3.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"2839254864795b7c420b9091b14758ab\"><img alt=\"Fig2 Sinard JPathologyInformatics2012 3.jpg\" src=\"https:\/\/www.limswiki.org\/images\/b\/b1\/Fig2_Sinard_JPathologyInformatics2012_3.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Table 2: Custom software development process<\/b><\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h3><span class=\"mw-headline\" id=\"Functional_specification\">Functional specification<\/span><\/h3>\n<p>The most important part of custom software development is preparation of the specifications document(s). These are often divided into functional specs and technical specs, but ideally can be combined into a single document depending on the scope of the project and the breath of knowledge of the individuals involved. If done sequentially, the functional specification has to come first, and is the more important of the two. If the functional specifications are not complete, thorough, and well conceived, a lot of wasted effort and re-engineering will be required later in the development process. The functional specs describe the look and feel of the software to be developed. It requires a clear understanding of what problem the software is supposed to solve, and how the solution will be used in the workflow. It is best if this document is prepared by a pathologist rather than by an \"IT\" person. It should not be a \"high-level\" document, but rather should be very specific, ideally down to diagrams of the screens and a description of what should happen when the user interacts with each control (button, checkbox, drop-down list, etc.) on the screen. End-users may not be able to conceptualize the application at this level. Rather, they will provide \"use-cases\", descriptions of when they would use the software and what they need it to do. The author of the functional specification then needs to take these use-cases into account, assimilate the information, and design an application that meets user's needs. The design should take into account where the software will be used (screen size, processor and memory requirements, space for other resources such as keyboard, mouse, and scanners). Finally, appropriate consideration needs to be given to whom the primary users are going to be, and that includes their likely skill set and personalities. What are the users willing to do? For example, if the designed software requires too many mouse clicks, too much typing, or has delays that routinely exceed half a second, many pathologists will be very resistant to adoption, and the solution may fail simply because users avoid using it. It is very useful if multiple potential users can review and have input on the functional specification, both to help assure the solution is general enough to be usable across multiple subspecialties (if appropriate) and to obtain greater buy-in from the user base.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Technical_specification\">Technical specification<\/span><\/h3>\n<p>When the functional specs are completed, the document can be handed-off to IT staff to develop the technical specification. Depending upon the scope of the project, multiple technical individuals with different areas of expertise may be appropriate (e.g., application developer and database designer). During this phase, the data structures will be developed and the overall architecture of the application will be designed. The most appropriate application delivery method (e.g., desktop application, client-server, web application) needs to be determined since this will affect the structure of the application. Typically, splitting the solution into modules is desirable, especially if the modules are independent enough that they can be developed and deployed gradually. The technical design phase also has to take into account the scalability of the application. How many total and\/or simultaneous users will there be? How much data will the application accumulate? These issues have implications for database table structure, indexing, memory requirements, etc. Finally, it might be a good idea, even at this phase, to consider the maintenance needs of the application. How much ongoing maintenance will be needed, and who will do it? For example, a solution that automatically files a high volume of material but requires manual intervention to process failed filing events will need ongoing resources for the manual processing.\n<\/p><p>In our environment, the majority of the specifications are combined, functional and technical, and are prepared by a pathologist with informatics experience. Specification documents can vary in length significantly based on the scope of the application, and ours have ranged from about five pages to over 100. The specification document(s), particularly the technical components, should be considered a dynamic document, and may have to be modified as the application is developed to fine-tune the final product.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Software_development\">Software development<\/span><\/h3>\n<p>The actual software writing is the most variable part of the development process. Individual programmers will have different skills, and different preferences for development platforms (operating system as well as integrated development environments) and programming languages. The use and integration of open-source frameworks and components can substantially facilitate this process, as well as mitigate many of the risks often associated with custom software development. OSS is software developed by self-selected groups of programmers and made available to the public for use, modification, and incorporation into their own solutions. Many OSS projects have some management infrastructure and follow formal process (e.g., Free Software Foundation, Apache Foundation, Mozilla Foundation, etc.). Typically, this software is available for free, but may carry some restrictions about future commercialization, which is usually not a problem for pathology departments developing custom solutions to problems because there is no intention to subsequently commercialize the product. There are thousands of OSS projects available for download at GNU Savannah (savannah.gnu.org), sourceforge.net, Google code, etc. Well-written solutions are very popular, and as such are extremely well tested and debugged by multiple users, and updates with new features and some bug fixes are routinely produced. OSS can include fully operational solutions (e.g., Linux operating system, <a href=\"https:\/\/www.limswiki.org\/index.php\/MySQL\" title=\"MySQL\" target=\"_blank\" class=\"wiki-link\" data-key=\"35005451bfcd508bce47c58e72260128\">MySQL<\/a> database, Apache Web Server, <a href=\"https:\/\/www.limswiki.org\/index.php\/Apache_Tomcat\" title=\"Apache Tomcat\" target=\"_blank\" class=\"wiki-link\" data-key=\"6fd6693ebebef576e0e80cf1c328d360\">Apache Tomcat<\/a>), development tools (e.g., Eclipse integrated development environment, Google Web Toolkit), as well as frameworks (Sprint, Hybernate, Quartz, etc.), component libraries and application programming interfaces (e.g., HAPI application programming interface, iText, jFreeChart, Apache Commons) that can be integrated into custom software such as <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_Level_Seven\" title=\"Health Level Seven\" class=\"mw-redirect wiki-link\" target=\"_blank\" data-key=\"c5b65d5af4e94435ec8a563c37fee00b\">HL7<\/a> engines, PDF generation, scheduling engines, and charting\/graphing solutions. Use of open-source components substantially mitigates the risks of custom software development because it markedly reduces the volume of code to be written, expedites development, and minimizes bugs and errors because significant portions of the solution have already been tested by a large number of users. You retain the ability to modify the software to meet your current or future needs.\n<\/p><p>There is substantial literature on Rapid Application Development, and various methodologies have been used to improve productivity and deliver working code to the end-user in the shortest amount of time, maintaining a balance between development time and the quality of the end product. The essence of these approaches is outlined in the Agile Software Development Manifesto.<sup id=\"rdp-ebb-cite_ref-BeckMan01_10-0\" class=\"reference\"><a href=\"#cite_note-BeckMan01-10\" rel=\"external_link\">[10]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-BeckTest03_11-0\" class=\"reference\"><a href=\"#cite_note-BeckTest03-11\" rel=\"external_link\">[11]<\/a><\/sup> It was critical for us to adopt these Agile Principles in our development process because the speed of implementation of new functionality is one of the key benefits of in-house code development. Open source, with its philosophy of \"release early, release often,\" feeds well into this methodology.<sup id=\"rdp-ebb-cite_ref-RaymondTheCath97_12-0\" class=\"reference\"><a href=\"#cite_note-RaymondTheCath97-12\" rel=\"external_link\">[12]<\/a><\/sup> This philosophy is typically well received in medical environments because users can see ongoing improvements and more importantly can provide feedback and input which may alter the direction of the project toward a superior final product.\n<\/p><p>Finally, developing custom software for clinical use obviously requires a \"test environment.\" The clinical mission of the department must go on, and cannot be compromised by the occasional runaway process and\/or system crash that invariably occurs during software development. As much as possible, the test environment should mimic the production environment.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Validation\">Validation<\/span><\/h3>\n<p>Custom software for clinical use should be treated like any other laboratory-developed test and appropriately validated before it is used in a clinical setting. Validation (not to be confused with autovalidation of test results) may be governed by regulatory statutes, and those need to be considered carefully (Note that while we hope the discussion here proves helpful, it should not in any way be considered a comprehensive evaluation of the current legal and regulatory environment surrounding software development for clinical use). The <a href=\"https:\/\/www.limswiki.org\/index.php\/Food_and_Drug_Administration\" title=\"Food and Drug Administration\" target=\"_blank\" class=\"wiki-link\" data-key=\"e2be8927071ac419c0929f7aa1ede7fe\">Food and Drug Administration<\/a> (FDA) of the United States Federal Government has oversight responsibility and authority for \"<a href=\"https:\/\/www.limswiki.org\/index.php\/Medical_device\" title=\"Medical device\" target=\"_blank\" class=\"wiki-link\" data-key=\"8e821122daa731f0fa8782fae57831fa\">medical devices<\/a>.\" Software integrated into medical devices has always, therefore, been regulated by the FDA. The FDA does consider LISs in general to be medical devices, but these have been exempt from the 510(k) approval process since June of 1988.<sup id=\"rdp-ebb-cite_ref-FDAGuidanceArch99_13-0\" class=\"reference\"><a href=\"#cite_note-FDAGuidanceArch99-13\" rel=\"external_link\">[13]<\/a><\/sup> In contrast, because of its charge to regulate blood products, the FDA in March of 1994 determined that any software used in healthcare \"for the maintenance of data that personnel use in making decisions regarding the suitability of donors and the release of blood or blood components for transfusion\" is required to undergo the 510(k) approval process.<sup id=\"rdp-ebb-cite_ref-FDASoft94_14-0\" class=\"reference\"><a href=\"#cite_note-FDASoft94-14\" rel=\"external_link\">[14]<\/a><\/sup> Given this requirement, development of any custom software that touches on blood product management should be approached cautiously. It is worth noting that in 2011, the FDA issued a new regulation pertaining to what they define as \"Medical Device Data Systems\" (MDDSs).<sup id=\"rdp-ebb-cite_ref-FDA_MDDS11_15-0\" class=\"reference\"><a href=\"#cite_note-FDA_MDDS11-15\" rel=\"external_link\">[15]<\/a><\/sup> This includes standalone software which stores and\/or displays data derived from medical devices. This new regulation reclassifies MDDSs from Class III devices to Class I devices, substantially softening the regulatory requirements for bringing these systems to market. Developers of such software, including healthcare facilities, are required to register and list with the FDA. With respect to custom software development for in-house use only, however, the Code of Federal Regulation which governs the operation of the FDA specifically defines as \"exempt from registration\" any \"licensed practitioners, including physicians, dentists, and optometrists, who manufacture or otherwise alter devices solely for use in their practice\" (21 CFR 807.65(d)).<sup id=\"rdp-ebb-cite_ref-21CFR807.65_16-0\" class=\"reference\"><a href=\"#cite_note-21CFR807.65-16\" rel=\"external_link\">[16]<\/a><\/sup> Thus, there does not appear to be any current requirement to notify the FDA if you are developing software for use within your own institution, but this does not exempt the developers from validating their software. Moreover, as laboratorians, pathologists recognize the value and need for good quality control practices in the generation and distribution of any data used for patient care. The FDA does provide some useful guidance in this regard. In their Laboratory Manual of Quality Policies under Test Methods and Validation, they state \"5.4.7.2 Computer Use: When computers or automated equipment are used for the acquisition, processing, recording, reporting, storage or retrieval of test data, if computer software is developed by the user, its development is documented in detail and algorithms are validated.\"<sup id=\"rdp-ebb-cite_ref-FDA_ORA_17-0\" class=\"reference\"><a href=\"#cite_note-FDA_ORA-17\" rel=\"external_link\">[17]<\/a><\/sup> Additionally, in 2002, the FDA released a guidance document entitled \"General Principles of Software Validation.\"<sup id=\"rdp-ebb-cite_ref-FDAGeneral02_18-0\" class=\"reference\"><a href=\"#cite_note-FDAGeneral02-18\" rel=\"external_link\">[18]<\/a><\/sup> This document defines software validation as: \"Confirmation by examination and provision of objective evidence that software specifications conform to user needs and intended uses, and that the particular requirements implemented through software can be consistently fulfilled (Section 3.1.2).\" The guidance document acknowledges that determining how much testing is \"enough\" is difficult and that a developer \"cannot test forever.\" Rather, the goal is to achieve a \"level of confidence that the [software] meets all requirements and user expectations.\"\n<\/p><p>From a very practical standpoint, the extent of the validation needed depends on what the software does. Does it create new data, or does it simply display data already captured\/created from other validated systems in a new way? Will it be immediately obvious to the user if the software is not functioning properly, or is there a risk that using the software could result in an inappropriate clinical action? The greater the risk, the more extensive the validation activities need to be. For low-risk solutions, end-users can be part of the validation process via pilot phases. Users typically will not \"accept\" software that does not do what it is supposed to do, especially if they know that that software was developed in-house and thus could be fixed. Finally, an important part of the validation process is documentation. This includes the initial design specifications, documentation within the code itself, documentation of testing, and detailed instructions of what changes are needed to the production environment for deployment.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Solution_deployment\">Solution deployment<\/span><\/h3>\n<p>Deployment strategies for custom software can vary significantly and are dependent upon the scope of the solution developed. Is the code a standalone solution, an integrated solution, or are there components of both? What kind of concurrency is required between the two? For example, if you have engineered a composite solution with some standalone software and some software integrated into your LIS, can the standalone component exist without the presence of the LIS integrated component, or do they both have to be deployed simultaneously? Once deployed, is use of the software optional (e.g., an alternate way of doing something) or is it integral (it now becomes the only way to do something)? Either way, the code ultimately needs to be transferred to and set up in the production environment, and this is a great opportunity to double-check the documentation you have developed to make sure it is complete. The documentation should include all the components of the solution and any changes needed in the production environment for the software to operate properly.\n<\/p><p>If the software can be kept somewhat isolated (i.e., its use is not required in the workflow), a pilot phase is strongly recommended. In this phase of the process, a select group of users is chosen to try out the software for some or all of their cases for a period of time. Whenever possible, this should include those pathologists involved in the functional design of the software. Important feedback can be obtained from using the software \"for real,\" and this may result in some modifications or update to improve the synergy with the workflow.\n<\/p><p>If the software cannot be kept isolated (i.e. its use, upon deployment, becomes required), then a back-out strategy needs to be developed in advance. What will you do if the software does not work as expected? It is usually not feasible to simply stop all work in the department while it is being fixed. There are times when deployment has no practical back-out strategy (such as upgrading the LIS to a new version), and in such instances it is typically prudent to perform the deployment on a weekend when there is less time pressure associated with returning the system to a fully operational status.\n<\/p><p>For large development projects with multiple modules, one may have to choose between deploying modules individually or all at once. A staged deployment is often preferable, since users seem to respond better to smaller, incremental changes than to complete workflow changes. One may also have to decide between applying a workflow change to a subset of the specimens initially, or to all of the specimens at the same time. While the former may seem to carry less risk, remember that you are then creating two different workflows (the new and the old) which are operating side-by-side in the same lab, and that can be more disruptive than applying the change to all specimens from the start.\n<\/p><p>User training is always advisable in advance of any deployment, although this can be harder to accomplish in practice than in theory. Users do not typically have a lot of spare time in their workday, and there can be little incentive to learning something new that is not immediately applicable. We have found it more effective to simply inform everyone well in advance (about a week), give the new users an overview of what the new workflow will look like, perhaps allow them to choose when would be the best day\/time for the deployment, and then provide significant on-site support at the time of the roll-out, with the developers and ideally the pilot users and functional designers present\/available to help answer questions (which often take the form of \"why do I have to do it this way?\" rather than \"what am I supposed to do next?\").\n<\/p><p>Careful monitoring of the performance of the new software is needed following deployment. Despite extensive testing, there is no way to adequately anticipate the variety of ways users will find to use the new software, and this may uncover subtle deficiencies in either the design or the development which have to be addressed. Remember that many users are pretty clever and may find ways around using the software as intended, especially if it sometimes does not work quite right. Users may identify problems, but simply work around them rather than notifying anyone. We have found it useful to remind users about a week after deployment that the development team needs to be informed of any unusual behavior or possible bugs. It is not an infrequent occurrence at our institution where, for example, a pathologist involved in the development notices weeks later when they are on service an issue with the software which, when queried, everyone acknowledges having noticed but no one made any attempt to notify the development team about.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Updates_and_enhancements\">Updates and enhancements<\/span><\/h3>\n<p>Invariably, small bugs will be identified in any custom software which need to be addressed, but the frequency of detection does drop-off quickly after the software has been used for a couple of weeks. Sometimes, developing and deploying what is thought to be the ideal solution provide a better understanding of the problem, and that better understanding may suggest modifications to the software to create a superior solution. More commonly, an onslaught of suggestions for additional improvement will arise, and this should be interpreted as a sign of great success. Having seen what it is possible to accomplish with custom software and the workflow improvements that can result, users are inspired to think of additional improvements that will provide even greater benefits. It is important to have a process for aggregating these suggestions, appropriately vetting them with the design team. Is this a general improvement, or something that satisfies the idiosyncrasies of an individual user? Does it move the solution in the desired direction, or backward closer to the original workflow? Is it a small change or a large one that will require substantial re-engineering? It is often valuable to allow the deployed software to incubate with users for a while before rapidly responding to requests for changes. However, once the developed software has stabilized in the workflow, new opportunities for even greater workflow enhancement can be explored. Once a solution has been developed, incremental additions can progressively expand the scope of the solution to solve additional, related problems. This flexibility and the capability to respond quickly as needs become better-understood or change, or as additional needs arise, without having to embark on a new series of vendor negotiations is one of the true values of custom software development.\n<\/p><p>From the developer perspective, there are two relatively common pitfalls to be avoided, and these depend on the personalities of the programmers. The first is to abandon ownership of the application too early. Developers tend to like to develop, not support. But support groups within the department or institution will not understand the new application. They will not know what it is supposed to do, and what it can do. Integral involvement of at least a portion of the development team with the initial users can be critical to proper use and acceptance of the new software. Additionally, if any unanticipated behavior of the new solution is uncovered, it is an opportunity for the developers to see that first hand within the real-life use of the application. The second pitfall which developers can fall into is to never abandon their application. Developers can become attached to the product of their efforts, and may take to repeated reworking and refactoring of their solution to make it a little better. Perhaps a little redesign of a particular routine will make it run a little faster, or make it a little more generalizable. These activities, which typically affect the \"back-end\" of the application but have no visible effect to the users or the functionality, need to be examined critically with respect to what value they are truly providing. Avoid the trap of updating the application each time a new version of a library or other tool becomes available because this can consume significant resources with minimal yield. Even after a number of years, some developers may wish to cling to their initial code beyond its practical viability. Five or so years after the initial writing, it may be faster, cheaper, and more reliable to rewrite the solution from scratch using new tools rather than trying to update prior code. The logic for the solution has already been developed and worked out and usually can be transferred directly to a new development environment with minimal modifications.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Project_leadership\">Project leadership<\/span><\/h3>\n<p>One aspect of software development that has been absent from this discussion is that of project leadership. This is largely because the software development team in our Pathology Informatics Unit is rather small (essentially three people) and the decision-making hierarchy is clear. For larger groups, however, it is important to have a single individual ultimately responsible for the application. This individual should approve any changes to the specifications during the development process. They need to understand all facets of the solution and the workflow in which it will be used, and have the clarity of thought to be able to anticipate the implications for how modifications to one part of the application will affect other parts.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusion\">Conclusion<\/span><\/h2>\n<p>Despite commonly voiced and exaggerated concerns over the costs and risks associated with custom software development, tremendous yields in productivity and efficiency can be achieved with relatively modest investments. Both the costs and the risks can be mitigated by incorporating OSS into the solution, and by having a well-structured development process. Having the right people involved is far more important than the number of people, and involvement of individuals with a deep knowledge of the workflows which may be affected is crucial to the success of the development process. Ultimately, software is a tool. That tool needs to fit your needs, your environment, and your workflow. That tool needs to be adaptable in a time frame consistent with the changing practice of clinical laboratories, and has to strategically advance the mission of the lab to provide the highest quality patient care. The focus should be not on how the tool comes into existence, but on the benefits obtained from its use. When commercially available solutions fall short of the needs, custom software development is a viable, often superior solution.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Source_of_support\">Source of support<\/span><\/h3>\n<p>None\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflict_of_interest\">Conflict of interest<\/span><\/h3>\n<p>None\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<ol class=\"references\">\n<li id=\"cite_note-SinardOver05-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SinardOver05_1-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sinard, J.H.; Mattie, M.E. (2005). \"Overcoming the limitations of integrated clinical digital imaging solutions\". <i>Archives of Pathology & Laboratory Medicine<\/i> <b>129<\/b> (9): 1118-26. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1043%2F1543-2165%282005%29129%5B1118%3AOTLOIC%5D2.0.CO%3B2\" target=\"_blank\">10.1043\/1543-2165(2005)129[1118:OTLOIC]2.0.CO;2<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16119983\" target=\"_blank\">16119983<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Overcoming+the+limitations+of+integrated+clinical+digital+imaging+solutions&rft.jtitle=Archives+of+Pathology+%26+Laboratory+Medicine&rft.aulast=Sinard%2C+J.H.%3B+Mattie%2C+M.E.&rft.au=Sinard%2C+J.H.%3B+Mattie%2C+M.E.&rft.date=2005&rft.volume=129&rft.issue=9&rft.pages=1118-26&rft_id=info:doi\/10.1043%2F1543-2165%282005%29129%5B1118%3AOTLOIC%5D2.0.CO%3B2&rft_id=info:pmid\/16119983&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SinardSemi09-2\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SinardSemi09_2-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sinard, J.H.; Gershkovich, P. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.archivesofpathology.org\/doi\/full\/10.1043\/1543-2165-133.7.1148\" target=\"_blank\">\"Semiautomated Archiving of Scanned Requisition Documents in Anatomic Pathology - Advancing Practice, Instruction, and Innovation Through Informatics (APIII 2008) Conference\"<\/a>. <i>Archives of Pathology & Laboratory Medicine<\/i> <b>133<\/b> (7): 1148-1165. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1043%2F1543-2165-133.7.1148\" target=\"_blank\">10.1043\/1543-2165-133.7.1148<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.archivesofpathology.org\/doi\/full\/10.1043\/1543-2165-133.7.1148\" target=\"_blank\">http:\/\/www.archivesofpathology.org\/doi\/full\/10.1043\/1543-2165-133.7.1148<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Semiautomated+Archiving+of+Scanned+Requisition+Documents+in+Anatomic+Pathology+-+Advancing+Practice%2C+Instruction%2C+and+Innovation+Through+Informatics+%28APIII+2008%29+Conference&rft.jtitle=Archives+of+Pathology+%26+Laboratory+Medicine&rft.aulast=Sinard%2C+J.H.%3B+Gershkovich%2C+P.&rft.au=Sinard%2C+J.H.%3B+Gershkovich%2C+P.&rft.date=2009&rft.volume=133&rft.issue=7&rft.pages=1148-1165&rft_id=info:doi\/10.1043%2F1543-2165-133.7.1148&rft_id=http%3A%2F%2Fwww.archivesofpathology.org%2Fdoi%2Ffull%2F10.1043%2F1543-2165-133.7.1148&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SinardInt10-3\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SinardInt10_3-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sinard, J.H.; Gershkovich, P. (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.archivesofpathology.org\/doi\/10.1043\/1543-2165-134.6.936\" target=\"_blank\">\"Integrating Digital Dictation and the Anatomic Pathology Laboratory Information System - Advancing Practice, Instruction, and Innovation Through Informatics (APIII 2009) Conference\"<\/a>. <i>Archives of Pathology & Laboratory Medicine<\/i> <b>134<\/b> (6): 936-948. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1043%2F1543-2165-134.6.936\" target=\"_blank\">10.1043\/1543-2165-134.6.936<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.archivesofpathology.org\/doi\/10.1043\/1543-2165-134.6.936\" target=\"_blank\">http:\/\/www.archivesofpathology.org\/doi\/10.1043\/1543-2165-134.6.936<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Integrating+Digital+Dictation+and+the+Anatomic+Pathology+Laboratory+Information+System+-+Advancing+Practice%2C+Instruction%2C+and+Innovation+Through+Informatics+%28APIII+2009%29+Conference&rft.jtitle=Archives+of+Pathology+%26+Laboratory+Medicine&rft.aulast=Sinard%2C+J.H.%3B+Gershkovich%2C+P.&rft.au=Sinard%2C+J.H.%3B+Gershkovich%2C+P.&rft.date=2010&rft.volume=134&rft.issue=6&rft.pages=936-948&rft_id=info:doi\/10.1043%2F1543-2165-134.6.936&rft_id=http%3A%2F%2Fwww.archivesofpathology.org%2Fdoi%2F10.1043%2F1543-2165-134.6.936&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SinardUse09-4\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SinardUse09_4-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sinard, J.H.; Gershkovich, P. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.archivesofpathology.org\/doi\/full\/10.1043\/1543-2165-133.7.1148\" target=\"_blank\">\"Use of a Repetitive Task Scheduling Engine for Workflow Automation and Rare Event Detection in a Clinical Environment - Advancing Practice, Instruction, and Innovation Through Informatics (APIII 2008) Conference\"<\/a>. <i>Archives of Pathology & Laboratory Medicine<\/i> <b>133<\/b> (7): 1148-1165. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1043%2F1543-2165-133.7.1148\" target=\"_blank\">10.1043\/1543-2165-133.7.1148<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.archivesofpathology.org\/doi\/full\/10.1043\/1543-2165-133.7.1148\" target=\"_blank\">http:\/\/www.archivesofpathology.org\/doi\/full\/10.1043\/1543-2165-133.7.1148<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Use+of+a+Repetitive+Task+Scheduling+Engine+for+Workflow+Automation+and+Rare+Event+Detection+in+a+Clinical+Environment+-+Advancing+Practice%2C+Instruction%2C+and+Innovation+Through+Informatics+%28APIII+2008%29+Conference&rft.jtitle=Archives+of+Pathology+%26+Laboratory+Medicine&rft.aulast=Sinard%2C+J.H.%3B+Gershkovich%2C+P.&rft.au=Sinard%2C+J.H.%3B+Gershkovich%2C+P.&rft.date=2009&rft.volume=133&rft.issue=7&rft.pages=1148-1165&rft_id=info:doi\/10.1043%2F1543-2165-133.7.1148&rft_id=http%3A%2F%2Fwww.archivesofpathology.org%2Fdoi%2Ffull%2F10.1043%2F1543-2165-133.7.1148&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-GeshkovichFSLink10-5\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-GeshkovichFSLink10_5-0\" rel=\"external_link\">5.0<\/a><\/sup> <sup><a href=\"#cite_ref-GeshkovichFSLink10_5-1\" rel=\"external_link\">5.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Gershkovich, P.; Mutnick, N.; Sinard, J.H. (September 2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule\" target=\"_blank\">\"FSLink-Frozen Section Management Software with Real-Time Communication with the OR\"<\/a>. <i>Association for Pathology Informatics, 2010 Annual Meeting, Boston, MA<\/i>. Association for Pathology Informatics<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule\" target=\"_blank\">http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=FSLink-Frozen+Section+Management+Software+with+Real-Time+Communication+with+the+OR&rft.atitle=Association+for+Pathology+Informatics%2C+2010+Annual+Meeting%2C+Boston%2C+MA&rft.aulast=Gershkovich%2C+P.%3B+Mutnick%2C+N.%3B+Sinard%2C+J.H.&rft.au=Gershkovich%2C+P.%3B+Mutnick%2C+N.%3B+Sinard%2C+J.H.&rft.date=September+2010&rft.pub=Association+for+Pathology+Informatics&rft_id=http%3A%2F%2Fwww.pathologyinformatics.com%2Fschedule%2Ffullschedule&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SinardHATHid10-6\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SinardHATHid10_6-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Sinard, J.H.; Mutnick, N.; Gershkovich, P. (September 2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule\" target=\"_blank\">\"Histology Asset Tracking: Hidden Practices and Their Consequences\"<\/a>. <i>Association for Pathology Informatics, 2010 Annual Meeting, Boston, MA<\/i>. Association for Pathology Informatics<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule\" target=\"_blank\">http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Histology+Asset+Tracking%3A++Hidden+Practices+and+Their+Consequences&rft.atitle=Association+for+Pathology+Informatics%2C+2010+Annual+Meeting%2C+Boston%2C+MA&rft.aulast=Sinard%2C+J.H.%3B+Mutnick%2C+N.%3B+Gershkovich%2C+P.&rft.au=Sinard%2C+J.H.%3B+Mutnick%2C+N.%3B+Gershkovich%2C+P.&rft.date=September+2010&rft.pub=Association+for+Pathology+Informatics&rft_id=http%3A%2F%2Fwww.pathologyinformatics.com%2Fschedule%2Ffullschedule&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SinardHATDash10-7\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SinardHATDash10_7-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Sinard, J.H.; Mutnick, N.; Gershkovich, P. (September 2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule\" target=\"_blank\">\"Histology Asset Tracking Dashboard: Real-Time Monitoring and Dynamic Work Lists\"<\/a>. <i>Association for Pathology Informatics, 2010 Annual Meeting, Boston, MA<\/i>. Association for Pathology Informatics<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule\" target=\"_blank\">http:\/\/www.pathologyinformatics.com\/schedule\/fullschedule<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Histology+Asset+Tracking+Dashboard%3A++Real-Time+Monitoring+and+Dynamic+Work+Lists&rft.atitle=Association+for+Pathology+Informatics%2C+2010+Annual+Meeting%2C+Boston%2C+MA&rft.aulast=Sinard%2C+J.H.%3B+Mutnick%2C+N.%3B+Gershkovich%2C+P.&rft.au=Sinard%2C+J.H.%3B+Mutnick%2C+N.%3B+Gershkovich%2C+P.&rft.date=September+2010&rft.pub=Association+for+Pathology+Informatics&rft_id=http%3A%2F%2Fwww.pathologyinformatics.com%2Fschedule%2Ffullschedule&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SinardFac11-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SinardFac11_8-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sinard, J.H.; Mutnick, N.; Gershkovich, P. (2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2011\/2\/1\/43\/85679\" target=\"_blank\">\"Facilitating Feedback and Education on the Hot Seat Rotation - Abstracts: Pathology Informatics 2011 Meeting\"<\/a>. <i>Journal of Pathology Informatics<\/i> <b>2<\/b>: 43. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3238568\/\" target=\"_blank\">PMC3238568<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2011\/2\/1\/43\/85679\" target=\"_blank\">http:\/\/www.jpathinformatics.org\/text.asp?2011\/2\/1\/43\/85679<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Facilitating+Feedback+and+Education+on+the+Hot+Seat+Rotation+-+Abstracts%3A+Pathology+Informatics+2011+Meeting&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Sinard%2C+J.H.%3B+Mutnick%2C+N.%3B+Gershkovich%2C+P.&rft.au=Sinard%2C+J.H.%3B+Mutnick%2C+N.%3B+Gershkovich%2C+P.&rft.date=2011&rft.volume=2&rft.pages=43&rft_id=info:pmc\/PMC3238568&rft_id=http%3A%2F%2Fwww.jpathinformatics.org%2Ftext.asp%3F2011%2F2%2F1%2F43%2F85679&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-MillsSoft83-9\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-MillsSoft83_9-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Mills, H.J. (1983). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/books.google.com\/books\/about\/Software_Productivity.html?id=-JdQAAAAMAAJ\" target=\"_blank\"><i>Software Productivity<\/i><\/a>. Little, Brown. pp. 274. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" target=\"_blank\">ISBN<\/a> 9780316573887<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/books.google.com\/books\/about\/Software_Productivity.html?id=-JdQAAAAMAAJ\" target=\"_blank\">https:\/\/books.google.com\/books\/about\/Software_Productivity.html?id=-JdQAAAAMAAJ<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Software+Productivity&rft.aulast=Mills%2C+H.J.&rft.au=Mills%2C+H.J.&rft.date=1983&rft.pages=pp.%26nbsp%3B274&rft.pub=Little%2C+Brown&rft.isbn=9780316573887&rft_id=https%3A%2F%2Fbooks.google.com%2Fbooks%2Fabout%2FSoftware_Productivity.html%3Fid%3D-JdQAAAAMAAJ&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-BeckMan01-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-BeckMan01_10-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Beck, K.; Bennekum, A.; Cockburn, A. et al. (2001). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.agilemanifesto.org\/\" target=\"_blank\">\"Manifesto for Agile Software Development\"<\/a>. Ward Cunningham<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.agilemanifesto.org\/\" target=\"_blank\">http:\/\/www.agilemanifesto.org\/<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 01 September 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Manifesto+for+Agile+Software+Development&rft.atitle=&rft.aulast=Beck%2C+K.%3B+Bennekum%2C+A.%3B+Cockburn%2C+A.+et+al.&rft.au=Beck%2C+K.%3B+Bennekum%2C+A.%3B+Cockburn%2C+A.+et+al.&rft.date=2001&rft.pub=Ward+Cunningham&rft_id=http%3A%2F%2Fwww.agilemanifesto.org%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-BeckTest03-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-BeckTest03_11-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Beck, K. (2003). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/books.google.com\/books\/about\/Test_driven_Development.html?id=gFgnde_vwMAC\" target=\"_blank\"><i>Test-Driven Development by Example<\/i><\/a>. Addison-Wesley Professional. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" target=\"_blank\">ISBN<\/a> 9780321146533<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/books.google.com\/books\/about\/Test_driven_Development.html?id=gFgnde_vwMAC\" target=\"_blank\">https:\/\/books.google.com\/books\/about\/Test_driven_Development.html?id=gFgnde_vwMAC<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Test-Driven+Development+by+Example&rft.aulast=Beck%2C+K.&rft.au=Beck%2C+K.&rft.date=2003&rft.pub=Addison-Wesley+Professional&rft.isbn=9780321146533&rft_id=https%3A%2F%2Fbooks.google.com%2Fbooks%2Fabout%2FTest_driven_Development.html%3Fid%3DgFgnde_vwMAC&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-RaymondTheCath97-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-RaymondTheCath97_12-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Raymond, E.S. (02 August 2002). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.catb.org\/~esr\/writings\/cathedral-bazaar\/cathedral-bazaar\/index.html\" target=\"_blank\">\"The Cathedral and the Bazaar\"<\/a>. Thyrsus Enterprises<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.catb.org\/~esr\/writings\/cathedral-bazaar\/cathedral-bazaar\/index.html\" target=\"_blank\">http:\/\/www.catb.org\/~esr\/writings\/cathedral-bazaar\/cathedral-bazaar\/index.html<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 18 August 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=The+Cathedral+and+the+Bazaar&rft.atitle=&rft.aulast=Raymond%2C+E.S.&rft.au=Raymond%2C+E.S.&rft.date=02+August+2002&rft.pub=Thyrsus+Enterprises&rft_id=http%3A%2F%2Fwww.catb.org%2F%7Eesr%2Fwritings%2Fcathedral-bazaar%2Fcathedral-bazaar%2Findex.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-FDAGuidanceArch99-13\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-FDAGuidanceArch99_13-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">US Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health (09 September 1999). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/web.archive.org\/web\/20110901191855\/http:\/\/www.fda.gov\/MedicalDevices\/DeviceRegulationandGuidance\/GuidanceDocuments\/ucm073778.htm\" target=\"_blank\">\"Guidance for Industry, FDA Reviewers and Compliance on Off-The-Shelf Software Use in Medical Devices\"<\/a>. Food and Drug Administration. pp. 16. Archived from <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.fda.gov\/medicaldevices\/deviceregulationandguidance\/guidancedocuments\/ucm073778.htm\" target=\"_blank\">the original<\/a> on 01 September 2012<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/web.archive.org\/web\/20110901191855\/http:\/\/www.fda.gov\/MedicalDevices\/DeviceRegulationandGuidance\/GuidanceDocuments\/ucm073778.htm\" target=\"_blank\">https:\/\/web.archive.org\/web\/20110901191855\/http:\/\/www.fda.gov\/MedicalDevices\/DeviceRegulationandGuidance\/GuidanceDocuments\/ucm073778.htm<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 01 September 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Guidance+for+Industry%2C+FDA+Reviewers+and+Compliance+on+Off-The-Shelf+Software+Use+in+Medical+Devices&rft.atitle=&rft.aulast=US+Department+of+Health+and+Human+Services%2C+Food+and+Drug+Administration%2C+Center+for+Devices+and+Radiological+Health&rft.au=US+Department+of+Health+and+Human+Services%2C+Food+and+Drug+Administration%2C+Center+for+Devices+and+Radiological+Health&rft.date=09+September+1999&rft.pages=pp.+16&rft.pub=Food+and+Drug+Administration&rft_id=https%3A%2F%2Fweb.archive.org%2Fweb%2F20110901191855%2Fhttp%3A%2F%2Fwww.fda.gov%2FMedicalDevices%2FDeviceRegulationandGuidance%2FGuidanceDocuments%2Fucm073778.htm&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-FDASoft94-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-FDASoft94_14-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">US Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (31 March 1994). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.fda.gov\/downloads\/Biologics\" target=\"_blank\">Blood Vaccines\/Guidance Compliance Regulatory Information\/Other Recommendations for Manufacturers\/Memorandum to Blood Establishments\/UCM062804.pdf \"Software Used in Blood Establishments\"<\/a> (PDF). Food and Drug Administration. pp. 3<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.fda.gov\/downloads\/Biologics\" target=\"_blank\">http:\/\/www.fda.gov\/downloads\/Biologics<\/a> Blood Vaccines\/Guidance Compliance Regulatory Information\/Other Recommendations for Manufacturers\/Memorandum to Blood Establishments\/UCM062804.pdf<\/span><span class=\"reference-accessdate\">. Retrieved 18 August 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Software+Used+in+Blood+Establishments&rft.atitle=&rft.aulast=US+Department+of+Health+and+Human+Services%2C+Food+and+Drug+Administration%2C+Center+for+Biologics+Evaluation+and+Research&rft.au=US+Department+of+Health+and+Human+Services%2C+Food+and+Drug+Administration%2C+Center+for+Biologics+Evaluation+and+Research&rft.date=31+March+1994&rft.pages=pp.+3&rft.pub=Food+and+Drug+Administration&rft_id=http%3A%2F%2Fwww.fda.gov%2Fdownloads%2FBiologics+Blood+Vaccines%2FGuidance+Compliance+Regulatory+Information%2FOther+Recommendations+for+Manufacturers%2FMemorandum+to+Blood+Establishments%2FUCM062804.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-FDA_MDDS11-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-FDA_MDDS11_15-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">US Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health (15 February 2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.fda.gov\/MedicalDevices\/ProductsandMedicalProcedures\/GeneralHospitalDevicesandSupplies\/MedicalDeviceDataSystems\/ucm251897.htm\" target=\"_blank\">\"MDDS Rule\"<\/a>. Food and Drug Administration<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.fda.gov\/MedicalDevices\/ProductsandMedicalProcedures\/GeneralHospitalDevicesandSupplies\/MedicalDeviceDataSystems\/ucm251897.htm\" target=\"_blank\">http:\/\/www.fda.gov\/MedicalDevices\/ProductsandMedicalProcedures\/GeneralHospitalDevicesandSupplies\/MedicalDeviceDataSystems\/ucm251897.htm<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 18 August 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=MDDS+Rule&rft.atitle=&rft.aulast=US+Department+of+Health+and+Human+Services%2C+Food+and+Drug+Administration%2C+Center+for+Devices+and+Radiological+Health&rft.au=US+Department+of+Health+and+Human+Services%2C+Food+and+Drug+Administration%2C+Center+for+Devices+and+Radiological+Health&rft.date=15+February+2011&rft.pub=Food+and+Drug+Administration&rft_id=http%3A%2F%2Fwww.fda.gov%2FMedicalDevices%2FProductsandMedicalProcedures%2FGeneralHospitalDevicesandSupplies%2FMedicalDeviceDataSystems%2Fucm251897.htm&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-21CFR807.65-16\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-21CFR807.65_16-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?fr=807.65\" target=\"_blank\">\"United States Code of Federal Regulations, Title 21, Part 807, Section 65\"<\/a>. Food and Drug Administration<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?fr=807.65\" target=\"_blank\">http:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?fr=807.65<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 01 September 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=United+States+Code+of+Federal+Regulations%2C+Title+21%2C+Part+807%2C+Section+65&rft.atitle=&rft.pub=Food+and+Drug+Administration&rft_id=http%3A%2F%2Fwww.accessdata.fda.gov%2Fscripts%2Fcdrh%2Fcfdocs%2Fcfcfr%2FCFRSearch.cfm%3Ffr%3D807.65&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-FDA_ORA-17\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-FDA_ORA_17-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">US Department of Health and Human Services, Food and Drug Administration, Office of Regulatory Affairs, Division of Field Science (2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.fda.gov\/ScienceResearch\/FieldScience\/LaboratoryManual\/\" target=\"_blank\">\"Vol. I. Section 5.4.7.2: Laboratory Manual of Quality Policies for ORA Regulatory Laboratories\"<\/a>. Food and Drug Administration. p. 33<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.fda.gov\/ScienceResearch\/FieldScience\/LaboratoryManual\/\" target=\"_blank\">http:\/\/www.fda.gov\/ScienceResearch\/FieldScience\/LaboratoryManual\/<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 01 September 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Vol.+I.+Section+5.4.7.2%3A+Laboratory+Manual+of+Quality+Policies+for+ORA+Regulatory+Laboratories&rft.atitle=&rft.aulast=US+Department+of+Health+and+Human+Services%2C+Food+and+Drug+Administration%2C+Office+of+Regulatory+Affairs%2C+Division+of+Field+Science&rft.au=US+Department+of+Health+and+Human+Services%2C+Food+and+Drug+Administration%2C+Office+of+Regulatory+Affairs%2C+Division+of+Field+Science&rft.date=2012&rft.pages=p.+33&rft.pub=Food+and+Drug+Administration&rft_id=http%3A%2F%2Fwww.fda.gov%2FScienceResearch%2FFieldScience%2FLaboratoryManual%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-FDAGeneral02-18\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-FDAGeneral02_18-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">US Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health (2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.fda.gov\/MedicalDevices\/DeviceRegulationandGuidance\/GuidanceDocuments\/ucm085281.htm\" target=\"_blank\">\"General Principles of Software Validation; Final Guidance for Industry and FDA Staff\"<\/a>. Food and Drug Administration. p. 6<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.fda.gov\/MedicalDevices\/DeviceRegulationandGuidance\/GuidanceDocuments\/ucm085281.htm\" target=\"_blank\">http:\/\/www.fda.gov\/MedicalDevices\/DeviceRegulationandGuidance\/GuidanceDocuments\/ucm085281.htm<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 01 September 2012<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=General+Principles+of+Software+Validation%3B+Final+Guidance+for+Industry+and+FDA+Staff&rft.atitle=&rft.aulast=US+Department+of+Health+and+Human+Services%2C+Food+and+Drug+Administration%2C+Center+for+Devices+and+Radiological+Health&rft.au=US+Department+of+Health+and+Human+Services%2C+Food+and+Drug+Administration%2C+Center+for+Devices+and+Radiological+Health&rft.date=2012&rft.pages=p.+6&rft.pub=Food+and+Drug+Administration&rft_id=http%3A%2F%2Fwww.fda.gov%2FMedicalDevices%2FDeviceRegulationandGuidance%2FGuidanceDocuments%2Fucm085281.htm&rfr_id=info:sid\/en.wikipedia.org:Journal:Custom_software_development_for_use_in_a_clinical_laboratory\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192206\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.462 seconds\nReal time usage: 0.491 seconds\nPreprocessor visited node count: 13863\/1000000\nPreprocessor generated node count: 34304\/1000000\nPost\u2010expand include size: 117667\/2097152 bytes\nTemplate argument size: 49514\/2097152 bytes\nHighest expansion depth: 15\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 456.520 1 - -total\n 79.57% 363.272 1 - Template:Reflist\n 66.94% 305.591 18 - Template:Citation\/core\n 38.65% 176.426 11 - Template:Cite_web\n 25.45% 116.179 5 - Template:Cite_journal\n 15.49% 70.723 1 - Template:Infobox_journal_article\n 14.97% 68.344 1 - Template:Infobox\n 8.72% 39.801 80 - Template:Infobox\/row\n 8.62% 39.353 2 - Template:Cite_book\n 3.62% 16.525 22 - Template:Citation\/make_link\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:8483-0!*!0!!en!5!* and timestamp 20181214192206 and revision id 24796\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Custom_software_development_for_use_in_a_clinical_laboratory\">https:\/\/www.limswiki.org\/index.php\/Journal:Custom_software_development_for_use_in_a_clinical_laboratory<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","54f8c03773fbcda29fa23c857f6a1159_images":["https:\/\/www.limswiki.org\/images\/5\/5f\/Fig1_Sinard_JPathologyInformatics2012_3.jpg","https:\/\/www.limswiki.org\/images\/b\/b1\/Fig2_Sinard_JPathologyInformatics2012_3.jpg"],"54f8c03773fbcda29fa23c857f6a1159_timestamp":1544815326,"b8605708462c7083aa1f73a384e9fe8c_type":"article","b8605708462c7083aa1f73a384e9fe8c_title":"STATegra EMS: An experiment management system for complex next-generation omics experiments (Hern\u00e1ndez-de-Diego et al. 2014)","b8605708462c7083aa1f73a384e9fe8c_url":"https:\/\/www.limswiki.org\/index.php\/Journal:STATegra_EMS:_An_experiment_management_system_for_complex_next-generation_omics_experiments","b8605708462c7083aa1f73a384e9fe8c_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:STATegra EMS: An experiment management system for complex next-generation omics experiments\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nSTATegra EMS: An experiment management system for complex next-generation omics experimentsJournal\n \nBMC Systems BiologyAuthor(s)\n \nHern\u00e1ndez-de-Diego, R.; Boix-Chova, N.; G\u00f3mez-Cabrero, D.; Tegner, J.; Abugessaisa, I.; Conesa, A.Author affiliation(s)\n \nCentro de Investigaci\u00f3n Pr\u00edncipe Felipe and the Karolinska InstitutePrimary contact\n \nNone givenYear published\n \n2014Volume and issue\n \n8(Suppl 2)Page(s)\n \nS9DOI\n \n10.1186\/1752-0509-8-S2-S9ISSN\n \n1752-0509Distribution license\n \nCreative Commons Attribution 2.0 GenericWebsite\n \nhttp:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-8-S2-S9Download\n \nhttp:\/\/bmcsystbiol.biomedcentral.com\/track\/pdf\/10.1186\/1752-0509-8-S2-S9 (PDF)\n\nContents\n\n1 Abstract \n2 Background \n3 Methods \n\n3.1 STATegra EMS architecture \n3.2 User administration \n3.3 Data specification \n\n\n4 Results \n\n4.1 Use case \n\n\n5 Conclusion \n6 Availability and requirements \n7 Declarations \n\n7.1 Acknowledgements \n7.2 Declarations \n7.3 Authors' contributions \n7.4 Competing interests \n\n\n8 References \n9 Notes \n\n\n\nAbstract \nHigh-throughput sequencing assays are now routinely used to study different aspects of genome organization. As decreasing costs and widespread availability of sequencing enable more laboratories to use sequencing assays in their research projects, the number of samples and replicates in these experiments can quickly grow to several dozens of samples and thus require standardized annotation, storage and management of preprocessing steps. As a part of the STATegra project, we have developed an Experiment Management System (EMS) for high throughput omics data that supports different types of sequencing-based assays such as RNA-seq, ChIP-seq, Methyl-seq, etc, as well as proteomics and metabolomics data. The STATegra EMS provides metadata annotation of experimental design, samples and processing pipelines, as well as storage of different types of data files, from raw data to ready-to-use measurements. The system has been developed to provide research laboratories with a freely-available, integrated system that offers a simple and effective way for experiment annotation and tracking of analysis procedures.\n\nBackground \nThe widespread availability of high-throughput sequencing techniques have importantly impacted genome research and reshaped the way we study genome function and structure. The rapidly decreasing costs of sequencing make these technologies affordable to small and medium size laboratories. Furthermore, the constant development of novel sequencing based assays, coined with the suffix -seq, expands the scope of cellular properties analyzable by high-throughput sequencing, with sequencing reads forming an underlying common data format. Today, virtually all nucleic acid omics methods traditionally based on microarrays have a -seq counterpart and many more have been made available recently. As a consequence, the possibility of running multiple sequencing-based experiments to measure different aspects of gene regulation and combining these with non-sequencing omics technologies such as proteomics and metabolomics has become practical.[1][2][3][4][5] For example, the ENCODE project combined ten major types of sequencing-based assays to unravel the complexity of genome architecture.[6] Many records can be found at the SRA archive that integrate multiple -seq technologies measured on the same samples and a PubMed search for NGS plus proteomics or metabolomics results in over hundred entries. Last but not least, one of the advantages of sequenced-based experiments is that they are equally applicable to the study of well-annotated model organisms as well as less-studied non-model organisms since little or no a priori genome knowledge is required.\nMoreover, sequencing-based assays come with new challenges for data processing and storage. The memory size requirements of a medium sequencing experiments exceeds the capacity of current regular workstations. At the same time, the analysis steps to go from raw to processed data are more complex and resource intensive. As the number of datasets grows, the need to properly store and track the data and their associated metadata becomes more pressing. For example, a medium-sized RNA-seq experiments ranging between 4 to 20 samples of 20 million reads each can take up to 40 GB of raw data and generate multiple Quality Control and intermediate processing step files of up to 200 to 500 GB. Laboratory Information and Management Systems (LIMS) or Sample Management Systems (SMS) are bioinformatics tools that aid experimentalists to organize samples and experimental procedures in a controlled and annotated fashion. There are several commercial and free dedicated LIMS that have been developed specifically for genotyping labs where thousand of samples are processed by automated pipelines and procedures are tightly standardized.[7][8][9] One popular LIMS for genomics is BASE.[10] This software includes a highly structured system for metadata annotation and a flexible architecture for defining experiments and incorporating analysis modules. However, BASE is currently restricted to the annotation of microarray experiments.\nSeveral laboratory information systems have been developed and implemented specifically for samples at sequencing facilities to manage the large volume of samples and data routinely handled by such services. Some of these have been made available to the scientific community or exported to other centers[11] published an extension of the Protein Information Management System (PIMS) for the Leeds University DNA sequencing facility designed to provide sample tracking both to users and operators. The system allows facility users to place orders and monitor the processing status of their samples while a different interface provides operators with a full control on the progression of the sequencing pipeline with automated connection to sequencing robots. The Leeds system supervises the whole procedure from sample submission to generation of fastq files but does not track the actual experimental characteristics of the sequenced samples or the post-processing of the raw data. Other solutions add to the tracking of sequencing samples analysis modules that execute some steps of the raw data processing such as Quality Control analysis or mapping to a reference genome. For example, the QUEST software[12] uses an experiment-resolved configuration file to store experiment metadata and execute predefined processing pipelines. Another example is NG6[13] an integrated NGS storage and processing environment where workflows can be easily defined and adapted to different data input formats. NG6 can be used interactively to generate intermediate analysis statistics and downloadable end results. Similarly, Scholtalbers et al. recently published a LIMS for the Galaxy platform that keeps track of input sample quality and organize flow cells.[14] By working within the Galaxy system, associated fastq files are readily available for processing using the platform's analysis resources. Another interesting package is the MADMAX system that considers multiple omics experiments by incorporating modules for microrarrays, metabolomics and genome annotation.[15] MADMAX uses an Oracle relational database to store sample and raw data, and links to common bioinformatics tools such as Blast or Bioconductor installed on a computer cluster to facilitate data analysis.\nWe describe the STATegra Experiment Management System (EMS), which is an information system for storage and annotation of complex NGS and omics experiments. In contrast to other solutions that put the focus on management of thousands of samples for core sequencing facilities, the STATegra EMS has as primary goal the annotation of experiments designed and run at individual research laboratories. The system contains modules for the definition of omics experiments, samples and analysis workflows and it is able to incorporate data from different analytical platforms and sequencing services with great flexibility. The STATegra EMS supports currently mRNA-seq, ChIP-seq, DNase-seq, Methyl-seq, miRNA-seq, Proteomics and Metabolomics by default and can be easily adapted to support additional high-throughput experiments. The system uses free, open source software technologies, such as Java Servlets, the Sencha EXT JS framework, MySQL relational database system and the Apache Tomcat Servlet engine. The application can be downloaded from http:\/\/stategra.eu\/\u200bstategraems.\n\nMethods \nSTATegra EMS architecture \nThe STATegra EMS was designed as a multiuser web application and is divided in two components: the SERVER SIDE application and the CLIENT SIDE web application (Figure 1).\n\n\n\n\n\n\n\n\n\n Figure 1. Overview of the STATegra EMS architecture\n\n\n\nThe server side is the responsible for keeping the consistency of data and for controlling the access to the stored information, is built using Java Servlets and a MySQL relational database and is unique for all clients. Although primarily designed and tested on Linux servers, the server EMS code could easily be adapted to work over other architectures due to the cross-platform nature of Java. Additionally, the server code was implemented using the Data Access Object design pattern in conjunction with the Data Transfer Object pattern. This provides an abstraction layer for interaction with databases that acts as an intermediary between server application (servlets) and the MySQL database, making easier future extensions of the application code with new features or changes in the database model.\nThe STATegra EMS client side was developed as user-friendly and intuitive web application using Ext JS, a cross-browser JavaScript framework which provided powerful tools for building interactive web applications. The client side is based on the Model-View-Controller architecture pattern, which make easier to organize, maintain and extend large client applications. Communication between Client and Server side is handled by AJAX and HTTP GET and POST protocols using JavaScript Object Notation (JSON) for data exchange.\n\nUser administration \nThe STATegra EMS is a system with user control. Users should be registered by the Administrator in the application before start working. As a general rule, the user creating a data element becomes the owner of this element and has exclusive rights for editing and deleting. However, any owner can grant access rights to other registered users of the system.\n\nData specification \nThe overall objective of the STATegra EMS is to serve as a logbook for high-throughput genomics projects performed at research labs by providing an easy-to-use tool for the annotation of experimental design, samples, measurements, and the analysis pipelines applied to the data. Experimental data and metadata are organized in the EMS around three major metadata modules (Figure 2): the Experiment module that records experimental design information and associated samples; the Samples module that collects all information on the used biomaterial; and the Analysis module that contains analysis pipelines and results. Both Sample and Analysis modules have been defined broadly to accommodate data from different type of omics experiments and still provide a common annotation framework. Commonly used standards in omics experimental data annotations were used when defining data specifications to facilitate EMS interoperability. In particular, we leveraged MIAPE[16] for proteomics analysis annotation (metabolomics guidelines proposed by Sumner et al.[17] and Goodacre et al.[18]) and MIAME[19] and MINSEQE[20] for sequencing experiments.\n\n\n\n\n\n\n\n\n\n Figure 2. Metadata Module structure in STATegra EMS. The Sample module stores information of biological conditions, biological replicates and the associated analytical samples. The analysis module contains all analysis steps from raw to processed data. Both samples and analyses are associated to one or more experiments within the Experiment module.\n\n\n\nSample and Analysis modules contain distinct Information Units (IUs), which are the basic elements of data input into the system and are connected by an experimental or analysis workflow. The Experiment Module is a wrapper of Samples and Analyses with one single data input form.\n(i) Experiment module: The experiment is the central unit of information of the STATegra EMS. An Experiment is defined by some scientific goals and a given experimental design that addresses these goals. This design implies a number of biological samples and an array of omics measurements, which are assigned to the Experiment.\n(ii) Sample module. This section hosts the information about biological conditions and their associated biological replicates and analytical samples. The IUs of this module are:\nBiological Condition. These are defined by the experimental design and consist of a given biological material such as the organism, cell type, tissue, etc. and, when applicable, an experimental condition such as treatment, dose or time-point for time-series samples.\nBiological Replicate. Each Biological Condition is assessed by using one or more biological replicates that may or may not correspond to the same experimental batch. The Biological Replicate stems directly from Biological Condition by adding a replicate number and, if applicable, a batch number.\nExperimental Batch. Frequently, when an experiment is composed of a large number of samples, only some of them can be generated at the same time. These samples correspond to the same batch. Batch information is relevant to identify systematic sources of noise that might affect all samples within the batch.\nAnalytical Sample. Omics experiments analyze molecular components of biological samples using a given experimental protocol with the resulting analytical sample ready-to-be-measured by the high-throughput techniques. For example, a RNA-seq analytical sample is obtained after using a cytosolic mRNA extraction protocol. Similarly for metabolomics, different analytical samples can be obtained by applying multiple extraction protocols that target distinct metabolic compounds.\n(iii) Analysis module. The Analysis module stores high-throughput molecular data obtained by the omics technologies and the data generated after processing of the primary raw data files. In contrast to the Sample module where only metadata is stored, the Analysis module also stores pointers to data files. The Analysis module consists of three data and one logical IUs:\nRaw Data. These files contain the data as produced by the omics equipment. For example, fastq files in the case of sequencing experiments and NMR .raw files in the case of metabolomics experiments. The Raw data IU also contains detailed information of the experimental protocol applied to the analytical sample, i.e., the library preparation protocol followed in a RNA-seq experiment or the NMR analysis characteristics in the case of metabolomics.\nIntermediate Data. This IU covers all processing steps from raw data to process data. Different omics experiment might require zero, one, or several intermediate steps. For example, in the case of RNA-seq, the mapping to a reference genome that produces a bam file constitutes an intermediate step. ChIP-seq will generally have two intermediate steps consisting of read mapping and peak calling.\nProcessed Data. The Processed data IU contains the final processing step that result in a data file containing the final signal values for the omics assay.\nAnalysis. The STATegra EMS includes an additional IU, the Analysis, which is constructed by connecting some of the previous data IUs to define a data processing workflow. Figure 3 shows a generic representation of the workflow elements used in sequencing data analyses. An Analysis will start on a raw data file obtained from a particular analytical sample, continue through one or several intermediate data files covering different processing steps (such as trimming, mapping, filtering, merging, etc), and finalize in a processed data file that contain the signal values of the omics features. Alternatively, an Analysis can take as input a processed data file and apply additional processing steps to render a higher-level processed data. For example, in DNase-seq analysis, a primary workflow would be to call DNase hypersensitivity regions (DHR) by applying a peak-calling algorithm to a BAM file of mapped reads (Figure 4A); whereas a secondary Analysis could involve merging DHR.bed files from N different samples to obtain a set of consolidated regions and then counting the number of reads of each sample in the consolidated region set to generate a per-sample signal value file (Figure 4B).\n\n\n\n\n\n\n\n\n\n Figure 3. STATegra EMS analysis workflow components. The workflow is linked to an analytical sample object and consists of raw, intermediate and processed data IUs.\n\n\n\n\n\n\n\n\n\n\n\n\n Figure 4. Example of primary and secondary workflow for a DNase-seq analysis. Primary workflow (a) involves calling DNase hypersensitivity regions (DHR) by applying a peak-calling algorithm to a BAM file of mapped reads whereas secondary workflow (b) involves merging of DHR.bed files from different samples to obtain a set of consolidated regions and then counting the number of reads of each sample in the consolidated region set to generate a per-sample signal value file.\n\n\n\nIn terms of data consistency, a unique Analysis ID is always associated to one Processed Data ID and describes the set of steps involved in obtaining that particular processed data. Moreover, an Analysis is always associated to one or more Experiments and, since the Analysis workflow can be traced back to raw data and its associated analytical samples, the Analysis provides the link between the Experiment and the Sample modules. By default, when a new Analysis is created, it will be assigned to the currently active Experiment. Figure 5 shows the data input window at the Analysis module. The central panel displays the input form for the different analysis steps, while at the bottom a graphical representation of the workflow allows easily monitoring the elements and structure of the Analysis.\n\r\n\n\n\n\n\n\n\n\n\n\n Figure 5. Analysis module input window\n\n\n\nResults \nUse case \nTo illustrate the usage and functionalities of the STATegra EMS, we consider the registration into the system of a subset of the ENCODE human dataset[21] comprising the four omics data types (mRNA-seq, ChIP-seq, DNase-seq and Proteomics) of two cell lines GM12878 and K562, with two biological replicates for most data types. ENCODE cell lines were regularly cultured in batches at data production labs to generate the samples for the different sequencing assays. In our example, we consider the utilization of one or several biological replicates from the same batch to obtain the analytical samples for ChIP-seq and proteomics experiments as depicted in Figure 6. An instance of the STATegra EMS with the ENCODE test data fully annotated into the system can be accessed at http:\/\/stategra.eu\/\u200bstategraems_\u200btest.\n\n\n\n\n\n\n\n\n\n Figure 6. Sample scheme for cell line K562 ENCODE user case data. See main text for description.\n\n\n\nAt the Experiment Module a new experiment is created by the Experiment owner who assigns registered users to it. The Experiment has a unique ID within the system along with some basic information such as goal, description, type of experiment, experimental design and planned omics measurement types. Check boxes next to each planned measurement are available to monitor the progress of the experiment. These are automatically checked when a matching Analysis is uploaded and assigned to the Experiment. Figure 7 shows the Experiment annotation for our use case: a human-readable name (ENCODE test) and description (STATegra EMS test experiment) are given for the experiment, and the basic experimental details are indicated: multiple conditions experiment type, two biological replicates and three omics types, mRNA-seq, ChIP-seq, DNase-seq and proteomics.\n\n\n\n\n\n\n\n\n\n Figure 7. Annotation details at Experiment module.\n\n\n\nUsers then fill the Sample Module input form (Figure 8). The first of four sections of this form includes fields for General information on the sample such as sample ID (auto_generated), sample name (K562 or GM12878) and title, which is a more extended description of the sample (Chronic myelogenous leukemia\/Lymphoblastoid). The second section of the form is used to describe the Biomaterial. For this use case, we entered the lymphocyte cell type from the blood tissue in human, with GM12878 as normal and K562 as cancer variation. The Experimental condition section is left blank in this example, since our cell lines did not receive any particular treatment. The next section records the associated Biological Replicates, where we can add items when more than one biological replicate is available for the same biological condition. For this user case, we created nine biological replicates to implement the scheme in Figure 6 and indicated the number for each replicate (i.e. #1), the corresponding batch when applicable, and its derived analytical samples. Analytical samples are characterized by an extraction protocol and a name. Multiple analytical replicates can be created for one biological replicate. For example, the RNA-seq data in our use case has one Analytical sample per each of the two biological replicates obtained with the Caltech long mRNA extraction protocol, while the proteomics data includes four analytical samples corresponding to each sub-cellular fraction (membrane fraction, cytosol, nucleus, mitochondria) (Figure 6).\n\n\n\n\n\n\n\n\n\n Figure 8. Sample form. The sample form provides fields to annotate biological condition details including data on the associated biological replicates and analytical samples.\n\n\n\nFinally, information about the processing workflows is incorporated in the Analysis module. While the use case involves four omics types, we will only describe the RNA-seq workflow in detail, as the Chip-seq, DNase and Proteomics workflows are conceptually similar.\nWithin the active experiment, a new Analysis is selected, indicating mRNA-seq as the analysis type. Clicking on the \"Annotate new step\" adds each new analysis step. At the beginning of an Analysis \"Raw Data\" is the only option available, which opens the Raw Data form. At this point the user selects an existing Analytical Sample ID to start annotating the library preparation details and sequencing characteristics of a particular sample. In our example, we would choose the Analytical Sample #1 corresponding to Biological Replicate #1 of the K562 cell line. Additionally we can indicate the location of the raw data fastq file in our system. In principle the EMS does not stores any raw or processed data files, and instead provides pointers to the location of these files. Once the Raw Data form is completed and saved, a graphical representation of the analysis workflow is created on the lower screen window of the Analysis Module (Figure 5). This workflow will grow with the subsequent analysis steps. After the Raw Data step is created, additional intermediate steps can be added. In our user case, the next intermediate step to add is the mapping of the reads to the human reference genome, where the user would indicate which raw data file was used and other parameters such a reference genome annotation file or mapping algorithm such as GENCODE hg19 and TopHat respectively. Other subsequent intermediate steps can be envisioned such as trimming, removal of duplicate reads, etc. The analysis workflow ends with a Processed Data step with a form that requires annotation of a previous intermediate or raw data steps. For RNA-seq, one Processed Data step could for example correspond to the Cufflinks gtf file with FPKMs. A completed Analysis can be partially reused and modified to create additional workflows such as one leading to a different Processed Data step. For example, the first two steps of the previous analysis workflow can be imported to create a new workflow having a different Processed Data step recording a junction's bed file obtained by TopHat.\n\nConclusion \nAs high-throughput sequencing costs decrease and new sequencing-based molecular assays become available more research laboratories incorporate the NGS technology as a tool to address their scientific goals. This is additionally promoted by the fact that high-throughput sequencing is also feasible in organisms with very little genome information. In a typical scenario, the researcher plans and outsources his\/her experiments to sequencing facilities that might vary over time or according to the specific NGS assay required. When sequencing results arrive and accumulate, a necessity arises to properly store and organize large datasets and their associated processing pipelines. The STATegra EMS has been conceived to provide a management solution in these cases. The architecture of the system was designed having in mind the situation at research labs, where multiple experiments are run, samples might be replicated of reused in successive experiments, and one same biomaterial source could be used for different types of NGS assays. For this, the Sample Module arranges annotation into three Information Units: biological condition, biological replicate and analytical sample allowing one to many relationships, which creates the flexibility to define complex sampling settings without duplication of information. Similarly, the Analysis module divides metadata annotation into steps that can be reused to create alternative analysis workflows. Finally, by allowing samples and analyses to belong to different experiments, the STATegra EMS can accommodate possible connections between experiments.\nThis architecture is substantially different from other information management solutions created for NGS data that are oriented to sequencing facilities, such as the Galaxy LIMS[14] which handles requests from users to the service, or the NG6[13] that controls the sequencing workflow at sequencing providers. In these cases the management system is adapted to the production pipeline at the sequencing center and applies a strong control on the facility wet-lab including library preparation and sequencer runs. This type of information is absent from the STATegra EMS, which may actually accept data from multiple sequencing providers. On the contrary the STATegra EMS records experimental information and sample metadata that might not be relevant at a production center. In conclusion, NGS LIMS and the STATegra EMS target different users and needs in the management of sequencing data. An open challenge is yet to optimize the integration of -seq data with clinical information similarly to what is done in clinical development centers.[22][23]\nThe current STATegra EMS supports analysis workflows for five popular sequencing functional assays but can easily be extended to other *seq applications as processing step forms are generic for DNA and cDNA high-throughput sequencing. Additionally, the system supports annotation of omics experiments targeting non nucleic acid components, such as proteomics and metabolomics for which specific input forms have been incorporated. All together, the STATegra EMS provides an integrated system for annotation of complex high-throughput omics experiments at functional genomics research laboratories.\n\nAvailability and requirements \nThe STATegra EMS application is distributed under GNU General Public License, Version 3 and can be obtained from http:\/\/stategra.eu\/\u200bstategraems. The STATegra EMS was developed in JAVA and is therefore platform independent, but it has only been extensively tested for UNIX environments. The software MySQL server and Apache Tomcat. Installation instructions can be found at http:\/\/stategra.eu\/\u200bstategraems_\u200binstallation.\n\nDeclarations \nAcknowledgements \nThe authors thank Ali Mortazavi for critical discussion of the manuscript. This work has been funded by the STATegra project, EU FP7 grant number 30600. This work was partially supported by COST-BMBS, Action BM1006 \"Next Generation Sequencing Data Analysis Network\", SeqAhead. The contribution of IA was also supported by \u00c5ke Wibergs Stiftelsen medicine research Diarienr: 719593091 (http:\/\/ake-wiberg.se\/\u200b).\n\nDeclarations \nThe publication costs for this article were funded by the STATegra project, EU FP7 grant number 30600.\nThis article has been published as part of BMC Systems Biology Volume 8 Supplement 2, 2014: Selected articles from the High-Throughput Omics and Data Integration Workshop. The full contents of the supplement are available online at http:\/\/www.biomedcentral.com\/\u200bbmcsystbiol\/\u200bsupplements\/\u200b8\/\u200bS2.\n\nAuthors' contributions \nRH conceived, implemented the STATegra EMS and helped drafting the manuscript. NBC helped implementing. IA, DGC and JT helped in conceiving the EMS. AC supervised the work and drafted the manuscript. All authors approved the final version of the manuscript.\n\nCompeting interests \nThe authors declare no conflicts of interests.\n\nReferences \n\n\n\u2191 Song, C.X.; Szulwach, K.E.; Dai, Q. et al. (2013). \"Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming\". Cell 153 (3): 678\u2013691. doi:10.1016\/j.cell.2013.04.001. PMC PMC3657391. PMID 23602153. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3657391 .   \n\n\u2191 Wei, G.; Abraham, B.J.; Yagi, R. et al. (2011). \"Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types\". Immunity 35 (2): 299\u2013311. doi:10.1016\/j.immuni.2011.08.007. PMC PMC3169184. PMID 21867929. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3169184 .   \n\n\u2191 Schmid, N.; Pessi, G.; Deng, Y. et al. (2012). \"The AHL- and BDSF-dependent quorum sensing systems control specific and overlapping sets of genes in Burkholderia cenocepacia H111\". PLoS One 7 (11): e49966. doi:10.1371\/journal.pone.0049966. PMC PMC3502180. PMID 23185499. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3502180 .   \n\n\u2191 Bordbar, A.; Mo, M.L.; Nakayasu, E.S. et al. (2012). \"Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation\". Molecular Systems Biology 8: 558. doi:10.1038\/msb.2012.21. PMC PMC3397418. PMID 22735334. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3397418 .   \n\n\u2191 Baltz, A.G.; Munschauer, M.; Schwanh\u00e4usser, B. et al. (2012). \"The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts\". Molecular Cell 46 (5): 674\u2013690. doi:10.1016\/j.molcel.2012.05.021. PMID 22681889.   \n\n\u2191 ENCODE Project Consortium; Bernstein, B.E.; Birney, E. et al. (2012). \"An integrated encyclopedia of DNA elements in the human genome\". Nature 489 (7414): 57\u201374. doi:10.1038\/nature11247. PMC PMC3439153. PMID 22955616. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3439153 .   \n\n\u2191 Van Rossum, T.; Tripp, B.; Daley, D. (2010). \"SLIMS: A user-friendly sample operations and inventory management system for genotyping labs\". Bioinformatics 26 (14): 1808-1810. doi:10.1093\/bioinformatics\/btq271. PMC PMC2894515. PMID 20513665. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2894515 .   \n\n\u2191 Binneck, E.; Silva, J.F.; Neumaier, N. et al. (2004). \"VSQual: A visual system to assist DNA sequencing quality control\". Genetics and Molecular Research 3 (4): 474\u2013482. PMID 15688314.   \n\n\u2191 Haquin, S.; Oeuillet, E.; Pajon, A. et al. (2008). \"Data management in structural genomics: an overview\". Methods in Molecular Biology 426: 49\u201379. doi:10.1007\/978-1-60327-058-8_4. PMID 18542857.   \n\n\u2191 Vallon-Christersson, J.; Nordborg, N.; Svensson, M.; H\u00e4kkinen, J. (2009). \"BASE - 2nd generation software for microarray data management and analysis\". BMC Bioinformatics 10: 330. doi:10.1186\/1471-2105-10-330. PMC PMC2768720. PMID 19822003. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2768720 .   \n\n\u2191 Troshin, P.V. Postis, V.L.; Ashworth, D. et al. (2011). \"PIMS sequencing extension: a laboratory information management system for DNA sequencing facilities\". BMC Research Notes 4: 48. doi:10.1186\/1756-0500-4-48. PMC PMC3058032. PMID 21385349. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3058032 .   \n\n\u2191 Camerlengo, T.; Ozer, H.G.; Onti-Srinivasan, R. et al. (2012). \"From sequencer to supercomputer: an automatic pipeline for managing and processing next generation sequencing data\". AMIA Joint Summits on Translational Science Proceedings 2012: 1\u201310. PMC PMC3392054. PMID 22779037. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3392054 .   \n\n\u2191 13.0 13.1 Mariette, J.; Escudi\u00e9, F.; Allias, N.; Salin, G.; Noirot, C.; Thomas, S.; Klopp, C. (2012). \"NG6: Integrated next generation sequencing storage and processing environment\". BMC Genomics 13: 462. doi:10.1186\/1471-2164-13-462. PMC PMC3444930. PMID 22958229. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3444930 .   \n\n\u2191 14.0 14.1 Scholtalbers, J.; R\u00f6ssler, J.; Sorn, P.; de Graaf, J.; Boisgu\u00e9rin, V.; Castle, J.; Sahin, U. (2013). \"Galaxy LIMS for next-generation sequencing\". Bioinformatics 29 (9): 1233-1234. doi:10.1093\/bioinformatics\/btt115. PMID 23479349.   \n\n\u2191 Lin, K.; Kools, H.; de Groot, P.J. et al. (2011). \"MADMAX - Management and analysis database for multiple omics experiments\". Journal of Integrative Bioinformatics 8 (2): 160. doi:10.2390\/biecoll-jib-2011-160. PMID 21778530.   \n\n\u2191 Taylor, C.F.; Paton, N.W.; Lilley, K.S. et al. (2007). \"The minimum information about a proteomics experiment (MIAPE)\". Nature Biotechnology 25 (8): 887-893. doi:10.1038\/nbt1329. PMID 17687369.   \n\n\u2191 Sumner, L.W.; Amberg, A.; Barrett, D. et al. (2007). \"Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI)\". Metabolomics 3 (3): 211\u2013221. doi:10.1007\/s11306-007-0082-2. PMC PMC3772505. PMID 24039616. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3772505 .   \n\n\u2191 Goodacre, R.; Broadhurst, D.; Smilde, A.K. et al. (2007). \"Proposed minimum reporting standards for data analysis in metabolomics\". Metabolomics 3 (3): 231\u2013241. doi:10.1007\/s11306-007-0081-3.   \n\n\u2191 Brazma, A.; Hingamp, P.; Quackenbush, J. et al. (2001). \"Minimum information about a microarray experiment (MIAME)-toward standards for microarray data\". Nature Genetics 29 (4): 365\u2014371. doi:10.1038\/ng1201-365. PMID 11726920.   \n\n\u2191 Functional Genomics Data Society. \"MINSEQE: Minimum Information about a high throughput Nucleotide SeQuencing Experiment\". fged.org. http:\/\/www.fged.org\/projects\/minseqe\/ .   \n\n\u2191 \"ENCODE Experiment Matrix\". UCSC. http:\/\/genome.ucsc.edu\/ENCODE\/dataMatrix\/encodeDataMatrixHuman.html .   \n\n\u2191 Abugessaisa, I.; Gomez-Cabrero, D.; Snir, O. et al. (2013). \"Implementation of the CDC translational informatics platform - from genetic variants to the National Swedish Rheumatology Quality Register\". Journal of Translational Medicine 11: 85. doi:10.1186\/1479-5876-11-85. PMC PMC3623742. PMID 23548156. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3623742 .   \n\n\u2191 Abugessaisa, I.; Saevarsdottir, S.; Tsipras, G. et al.. \"Integrating Clinically Driven Development with suitable Database Architecture in Assembling an Informatics Fusion Platform to Accelerate Translational Research\". (Submitted to) Science Translational Medicine.   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. References 17 and 18 were not attached to any text in the original, so author names were added to the text for better flow.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:STATegra_EMS:_An_experiment_management_system_for_complex_next-generation_omics_experiments\">https:\/\/www.limswiki.org\/index.php\/Journal:STATegra_EMS:_An_experiment_management_system_for_complex_next-generation_omics_experiments<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on bioinformatics\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 15 March 2016, at 00:25.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 1,655 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","b8605708462c7083aa1f73a384e9fe8c_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_STATegra_EMS_An_experiment_management_system_for_complex_next-generation_omics_experiments skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:STATegra EMS: An experiment management system for complex next-generation omics experiments<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>High-throughput <a href=\"https:\/\/www.limswiki.org\/index.php\/Sequencing\" title=\"Sequencing\" class=\"mw-disambig wiki-link\" target=\"_blank\" data-key=\"e36167a9eb152ca16a0c4c4e6d13f323\">sequencing<\/a> assays are now routinely used to study different aspects of genome organization. As decreasing costs and widespread availability of sequencing enable more <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" target=\"_blank\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratories<\/a> to use sequencing assays in their research projects, the number of samples and replicates in these experiments can quickly grow to several dozens of samples and thus require standardized <a href=\"https:\/\/www.limswiki.org\/index.php\/Genome_informatics\" title=\"Genome informatics\" target=\"_blank\" class=\"wiki-link\" data-key=\"304bd6698e9a01cab6157ba518743ff1\">annotation, storage and management<\/a> of preprocessing steps. As a part of the STATegra project, we have developed an Experiment Management System (EMS) for high throughput omics data that supports different types of sequencing-based assays such as RNA-seq, ChIP-seq, Methyl-seq, etc, as well as proteomics and metabolomics data. The STATegra EMS provides metadata annotation of experimental design, samples and processing pipelines, as well as storage of different types of data files, from raw data to ready-to-use measurements. The system has been developed to provide research laboratories with a freely-available, integrated system that offers a simple and effective way for experiment annotation and tracking of analysis procedures.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Background\">Background<\/span><\/h2>\n<p>The widespread availability of high-throughput sequencing techniques have importantly impacted <a href=\"https:\/\/www.limswiki.org\/index.php\/Genomics\" title=\"Genomics\" target=\"_blank\" class=\"wiki-link\" data-key=\"96a82dabf51cf9510dd00c5a03396c44\">genome<\/a> research and reshaped the way we study genome function and structure. The rapidly decreasing costs of sequencing make these technologies affordable to small and medium size laboratories. Furthermore, the constant development of novel sequencing based assays, coined with the suffix -<i>seq<\/i>, expands the scope of cellular properties analyzable by high-throughput sequencing, with sequencing reads forming an underlying common data format. Today, virtually all nucleic acid omics methods traditionally based on microarrays have a -<i>seq<\/i> counterpart and many more have been made available recently. As a consequence, the possibility of running multiple sequencing-based experiments to measure different aspects of gene regulation and combining these with non-sequencing omics technologies such as proteomics and metabolomics has become practical.<sup id=\"rdp-ebb-cite_ref-SongGenome13_1-0\" class=\"reference\"><a href=\"#cite_note-SongGenome13-1\" rel=\"external_link\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-WeiGenome11_2-0\" class=\"reference\"><a href=\"#cite_note-WeiGenome11-2\" rel=\"external_link\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-SchmidTheAHL12_3-0\" class=\"reference\"><a href=\"#cite_note-SchmidTheAHL12-3\" rel=\"external_link\">[3]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-BordbarModel12_4-0\" class=\"reference\"><a href=\"#cite_note-BordbarModel12-4\" rel=\"external_link\">[4]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-BaltzThe_mRNA12_5-0\" class=\"reference\"><a href=\"#cite_note-BaltzThe_mRNA12-5\" rel=\"external_link\">[5]<\/a><\/sup> For example, the ENCODE project combined ten major types of sequencing-based assays to unravel the complexity of genome architecture.<sup id=\"rdp-ebb-cite_ref-ENCODEAnInt12_6-0\" class=\"reference\"><a href=\"#cite_note-ENCODEAnInt12-6\" rel=\"external_link\">[6]<\/a><\/sup> Many records can be found at the SRA archive that integrate multiple -<i>seq<\/i> technologies measured on the same samples and a PubMed search for NGS plus proteomics or metabolomics results in over hundred entries. Last but not least, one of the advantages of sequenced-based experiments is that they are equally applicable to the study of well-annotated model organisms as well as less-studied non-model organisms since little or no <i>a priori<\/i> genome knowledge is required.\n<\/p><p>Moreover, sequencing-based assays come with new challenges for data processing and storage. The memory size requirements of a medium sequencing experiments exceeds the capacity of current regular workstations. At the same time, the analysis steps to go from raw to processed data are more complex and resource intensive. As the number of datasets grows, the need to properly store and track the data and their associated metadata becomes more pressing. For example, a medium-sized RNA-seq experiments ranging between 4 to 20 samples of 20 million reads each can take up to 40 GB of raw data and generate multiple Quality Control and intermediate processing step files of up to 200 to 500 GB. <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" target=\"_blank\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">Laboratory Information and Management Systems<\/a> (LIMS) or Sample Management Systems (SMS) are <a href=\"https:\/\/www.limswiki.org\/index.php\/Bioinformatics\" title=\"Bioinformatics\" target=\"_blank\" class=\"wiki-link\" data-key=\"8f506695fdbb26e3f314da308f8c053b\">bioinformatics<\/a> tools that aid experimentalists to organize samples and experimental procedures in a controlled and annotated fashion. There are several commercial and free dedicated LIMS that have been developed specifically for genotyping labs where thousand of samples are processed by automated pipelines and procedures are tightly standardized.<sup id=\"rdp-ebb-cite_ref-VanRossumSLIMS10_7-0\" class=\"reference\"><a href=\"#cite_note-VanRossumSLIMS10-7\" rel=\"external_link\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-BinneckVS04_8-0\" class=\"reference\"><a href=\"#cite_note-BinneckVS04-8\" rel=\"external_link\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-HaquinData08_9-0\" class=\"reference\"><a href=\"#cite_note-HaquinData08-9\" rel=\"external_link\">[9]<\/a><\/sup> One popular LIMS for genomics is <a href=\"https:\/\/www.limswiki.org\/index.php\/BASE\" title=\"BASE\" target=\"_blank\" class=\"wiki-link\" data-key=\"36231d20d7206b3d9d0ca18dff0aac02\">BASE<\/a>.<sup id=\"rdp-ebb-cite_ref-VallonBASE09_10-0\" class=\"reference\"><a href=\"#cite_note-VallonBASE09-10\" rel=\"external_link\">[10]<\/a><\/sup> This software includes a highly structured system for metadata annotation and a flexible architecture for defining experiments and incorporating analysis modules. However, BASE is currently restricted to the annotation of microarray experiments.\n<\/p><p>Several laboratory information systems have been developed and implemented specifically for samples at sequencing facilities to manage the large volume of samples and data routinely handled by such services. Some of these have been made available to the scientific community or exported to other centers<sup id=\"rdp-ebb-cite_ref-TroshinPIMS11_11-0\" class=\"reference\"><a href=\"#cite_note-TroshinPIMS11-11\" rel=\"external_link\">[11]<\/a><\/sup> published an extension of the <a href=\"https:\/\/www.limswiki.org\/index.php\/PiMS\" title=\"PiMS\" target=\"_blank\" class=\"wiki-link\" data-key=\"aa61d8159c6d0a8f4cdeca09d397701f\">Protein Information Management System<\/a> (PIMS) for the Leeds University DNA sequencing facility designed to provide sample tracking both to users and operators. The system allows facility users to place orders and monitor the processing status of their samples while a different interface provides operators with a full control on the progression of the sequencing pipeline with automated connection to sequencing robots. The Leeds system supervises the whole procedure from sample submission to generation of fastq files but does not track the actual experimental characteristics of the sequenced samples or the post-processing of the raw data. Other solutions add to the tracking of sequencing samples analysis modules that execute some steps of the raw data processing such as Quality Control analysis or mapping to a reference genome. For example, the QUEST software<sup id=\"rdp-ebb-cite_ref-CamerlengoFrom12_12-0\" class=\"reference\"><a href=\"#cite_note-CamerlengoFrom12-12\" rel=\"external_link\">[12]<\/a><\/sup> uses an experiment-resolved configuration file to store experiment metadata and execute predefined processing pipelines. Another example is NG6<sup id=\"rdp-ebb-cite_ref-MarietteNG612_13-0\" class=\"reference\"><a href=\"#cite_note-MarietteNG612-13\" rel=\"external_link\">[13]<\/a><\/sup> an integrated NGS storage and processing environment where workflows can be easily defined and adapted to different data input formats. NG6 can be used interactively to generate intermediate analysis statistics and downloadable end results. Similarly, Scholtalbers et al. recently published a LIMS for the <a href=\"https:\/\/www.limswiki.org\/index.php\/Galaxy_(biomedical_software)\" title=\"Galaxy (biomedical software)\" target=\"_blank\" class=\"wiki-link\" data-key=\"ead5d6ebaa8d67744d2f68d454d89ce6\">Galaxy<\/a> platform that keeps track of input sample quality and organize flow cells.<sup id=\"rdp-ebb-cite_ref-ScholtalbersGal13_14-0\" class=\"reference\"><a href=\"#cite_note-ScholtalbersGal13-14\" rel=\"external_link\">[14]<\/a><\/sup> By working within the Galaxy system, associated fastq files are readily available for processing using the platform's analysis resources. Another interesting package is the MADMAX system that considers multiple omics experiments by incorporating modules for microrarrays, metabolomics and genome annotation.<sup id=\"rdp-ebb-cite_ref-LinMAD11_15-0\" class=\"reference\"><a href=\"#cite_note-LinMAD11-15\" rel=\"external_link\">[15]<\/a><\/sup> MADMAX uses an Oracle relational database to store sample and raw data, and links to common bioinformatics tools such as Blast or Bioconductor installed on a computer cluster to facilitate data analysis.\n<\/p><p>We describe the STATegra Experiment Management System (EMS), which is an information system for storage and annotation of complex NGS and omics experiments. In contrast to other solutions that put the focus on management of thousands of samples for core sequencing facilities, the STATegra EMS has as primary goal the annotation of experiments designed and run at individual research laboratories. The system contains modules for the definition of omics experiments, samples and analysis workflows and it is able to incorporate data from different analytical platforms and sequencing services with great flexibility. The STATegra EMS supports currently mRNA-seq, ChIP-seq, DNase-seq, Methyl-seq, miRNA-seq, Proteomics and Metabolomics by default and can be easily adapted to support additional high-throughput experiments. The system uses free, open source software technologies, such as Java Servlets, the Sencha EXT JS framework, <a href=\"https:\/\/www.limswiki.org\/index.php\/MySQL\" title=\"MySQL\" target=\"_blank\" class=\"wiki-link\" data-key=\"35005451bfcd508bce47c58e72260128\">MySQL<\/a> relational database system and the <a href=\"https:\/\/www.limswiki.org\/index.php\/Apache_Tomcat\" title=\"Apache Tomcat\" target=\"_blank\" class=\"wiki-link\" data-key=\"6fd6693ebebef576e0e80cf1c328d360\">Apache Tomcat<\/a> Servlet engine. The application can be downloaded from <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/stategra.eu\/\u200bstategraems\" target=\"_blank\">http:\/\/stategra.eu\/\u200bstategraems<\/a>.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Methods\">Methods<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"STATegra_EMS_architecture\">STATegra EMS architecture<\/span><\/h3>\n<p>The STATegra EMS was designed as a multiuser web application and is divided in two components: the SERVER SIDE application and the CLIENT SIDE web application (Figure 1).\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"6743047fc7c496fa0e8d738b10e8155e\"><img alt=\"Fig1 Hernandez BMCSystemsBiology2014 8-Suppl2.jpg\" src=\"https:\/\/www.limswiki.org\/images\/c\/c9\/Fig1_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 1.<\/b> Overview of the STATegra EMS architecture<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>The server side is the responsible for keeping the consistency of data and for controlling the access to the stored <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" target=\"_blank\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a>, is built using Java Servlets and a MySQL relational database and is unique for all clients. Although primarily designed and tested on Linux servers, the server EMS code could easily be adapted to work over other architectures due to the cross-platform nature of Java. Additionally, the server code was implemented using the Data Access Object design pattern in conjunction with the Data Transfer Object pattern. This provides an abstraction layer for interaction with databases that acts as an intermediary between server application (servlets) and the MySQL database, making easier future extensions of the application code with new features or changes in the database model.\n<\/p><p>The STATegra EMS client side was developed as user-friendly and intuitive web application using Ext JS, a cross-browser JavaScript framework which provided powerful tools for building interactive web applications. The client side is based on the Model-View-Controller architecture pattern, which make easier to organize, maintain and extend large client applications. Communication between Client and Server side is handled by AJAX and HTTP GET and POST protocols using JavaScript Object Notation (JSON) for data exchange.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"User_administration\">User administration<\/span><\/h3>\n<p>The STATegra EMS is a system with user control. Users should be registered by the Administrator in the application before start working. As a general rule, the user creating a data element becomes the owner of this element and has exclusive rights for editing and deleting. However, any owner can grant access rights to other registered users of the system.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Data_specification\">Data specification<\/span><\/h3>\n<p>The overall objective of the STATegra EMS is to serve as a logbook for high-throughput genomics projects performed at research labs by providing an easy-to-use tool for the annotation of experimental design, samples, measurements, and the analysis pipelines applied to the data. Experimental data and metadata are organized in the EMS around three major metadata modules (Figure 2): the Experiment module that records experimental design information and associated samples; the Samples module that collects all information on the used <a href=\"https:\/\/www.limswiki.org\/index.php\/Biomaterial\" title=\"Biomaterial\" target=\"_blank\" class=\"wiki-link\" data-key=\"af680bf337e2578f3ed5d787dc411655\">biomaterial<\/a>; and the Analysis module that contains analysis pipelines and results. Both Sample and Analysis modules have been defined broadly to accommodate data from different type of omics experiments and still provide a common annotation framework. Commonly used standards in omics experimental data annotations were used when defining data specifications to facilitate EMS interoperability. In particular, we leveraged MIAPE<sup id=\"rdp-ebb-cite_ref-TaylorTheMin07_16-0\" class=\"reference\"><a href=\"#cite_note-TaylorTheMin07-16\" rel=\"external_link\">[16]<\/a><\/sup> for proteomics analysis annotation (metabolomics guidelines proposed by Sumner et al.<sup id=\"rdp-ebb-cite_ref-SumnerProposed07_17-0\" class=\"reference\"><a href=\"#cite_note-SumnerProposed07-17\" rel=\"external_link\">[17]<\/a><\/sup> and Goodacre et al.<sup id=\"rdp-ebb-cite_ref-GoodacreProp07_18-0\" class=\"reference\"><a href=\"#cite_note-GoodacreProp07-18\" rel=\"external_link\">[18]<\/a><\/sup>) and MIAME<sup id=\"rdp-ebb-cite_ref-BrazmaMin01_19-0\" class=\"reference\"><a href=\"#cite_note-BrazmaMin01-19\" rel=\"external_link\">[19]<\/a><\/sup> and MINSEQE<sup id=\"rdp-ebb-cite_ref-TheFuncMINSEQE12_20-0\" class=\"reference\"><a href=\"#cite_note-TheFuncMINSEQE12-20\" rel=\"external_link\">[20]<\/a><\/sup> for sequencing experiments.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"6d1a4cfb79f027ef93c163c40a85557a\"><img alt=\"Fig2 Hernandez BMCSystemsBiology2014 8-Suppl2.jpg\" src=\"https:\/\/www.limswiki.org\/images\/b\/b4\/Fig2_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 2. Metadata Module structure in STATegra EMS.<\/b> The Sample module stores information of biological conditions, biological replicates and the associated analytical samples. The analysis module contains all analysis steps from raw to processed data. Both samples and analyses are associated to one or more experiments within the Experiment module.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>Sample and Analysis modules contain distinct Information Units (IUs), which are the basic elements of data input into the system and are connected by an experimental or analysis workflow. The Experiment Module is a wrapper of Samples and Analyses with one single data input form.\n<\/p><p>(i) Experiment module: The experiment is the central unit of information of the STATegra EMS. An Experiment is defined by some scientific goals and a given experimental design that addresses these goals. This design implies a number of biological samples and an array of omics measurements, which are assigned to the Experiment.\n<\/p><p>(ii) Sample module. This section hosts the information about biological conditions and their associated biological replicates and analytical samples. The IUs of this module are:\n<\/p><p><i>Biological Condition<\/i>. These are defined by the experimental design and consist of a given biological material such as the organism, cell type, tissue, etc. and, when applicable, an experimental condition such as treatment, dose or time-point for time-series samples.\n<\/p><p><i>Biological Replicate<\/i>. Each Biological Condition is assessed by using one or more biological replicates that may or may not correspond to the same experimental batch. The Biological Replicate stems directly from Biological Condition by adding a replicate number and, if applicable, a batch number.\n<\/p><p><i>Experimental Batch<\/i>. Frequently, when an experiment is composed of a large number of samples, only some of them can be generated at the same time. These samples correspond to the same batch. Batch information is relevant to identify systematic sources of noise that might affect all samples within the batch.\n<\/p><p><i>Analytical Sample<\/i>. Omics experiments analyze molecular components of biological samples using a given experimental protocol with the resulting analytical sample ready-to-be-measured by the high-throughput techniques. For example, a RNA-seq analytical sample is obtained after using a cytosolic mRNA extraction protocol. Similarly for metabolomics, different analytical samples can be obtained by applying multiple extraction protocols that target distinct metabolic compounds.\n<\/p><p>(iii) Analysis module. The Analysis module stores high-throughput molecular data obtained by the omics technologies and the data generated after processing of the primary raw data files. In contrast to the Sample module where only metadata is stored, the Analysis module also stores pointers to data files. The Analysis module consists of three data and one logical IUs:\n<\/p><p><i>Raw Data<\/i>. These files contain the data as produced by the omics equipment. For example, fastq files in the case of sequencing experiments and NMR .raw files in the case of metabolomics experiments. The Raw data IU also contains detailed information of the experimental protocol applied to the analytical sample, i.e., the library preparation protocol followed in a RNA-seq experiment or the NMR analysis characteristics in the case of metabolomics.\n<\/p><p><i>Intermediate Data<\/i>. This IU covers all processing steps from raw data to process data. Different omics experiment might require zero, one, or several intermediate steps. For example, in the case of RNA-seq, the mapping to a reference genome that produces a bam file constitutes an intermediate step. ChIP-seq will generally have two intermediate steps consisting of read mapping and peak calling.\n<\/p><p><i>Processed Data<\/i>. The Processed data IU contains the final processing step that result in a data file containing the final signal values for the omics assay.\n<\/p><p><i>Analysis<\/i>. The STATegra EMS includes an additional IU, the Analysis, which is constructed by connecting some of the previous data IUs to define a data processing workflow. Figure 3 shows a generic representation of the workflow elements used in sequencing data analyses. An Analysis will start on a raw data file obtained from a particular analytical sample, continue through one or several intermediate data files covering different processing steps (such as trimming, mapping, filtering, merging, etc), and finalize in a processed data file that contain the signal values of the omics features. Alternatively, an Analysis can take as input a processed data file and apply additional processing steps to render a higher-level processed data. For example, in DNase-seq analysis, a primary workflow would be to call DNase hypersensitivity regions (DHR) by applying a peak-calling algorithm to a BAM file of mapped reads (Figure 4A); whereas a secondary Analysis could involve merging DHR.bed files from N different samples to obtain a set of consolidated regions and then counting the number of reads of each sample in the consolidated region set to generate a per-sample signal value file (Figure 4B).\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"b2d2084de8b6afa5f4a7b90034903ce8\"><img alt=\"Fig3 Hernandez BMCSystemsBiology2014 8-Suppl2.jpg\" src=\"https:\/\/www.limswiki.org\/images\/3\/3c\/Fig3_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 3. STATegra EMS analysis workflow components.<\/b> The workflow is linked to an analytical sample object and consists of raw, intermediate and processed data IUs.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"96a5cb2a00730c9f1bc249056174415e\"><img alt=\"Fig4 Hernandez BMCSystemsBiology2014 8-Suppl2.jpg\" src=\"https:\/\/www.limswiki.org\/images\/5\/5f\/Fig4_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 4. Example of primary and secondary workflow for a DNase-seq analysis.<\/b> Primary workflow (a) involves calling DNase hypersensitivity regions (DHR) by applying a peak-calling algorithm to a BAM file of mapped reads whereas secondary workflow (b) involves merging of DHR.bed files from different samples to obtain a set of consolidated regions and then counting the number of reads of each sample in the consolidated region set to generate a per-sample signal value file.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>In terms of data consistency, a unique Analysis ID is always associated to one Processed Data ID and describes the set of steps involved in obtaining that particular processed data. Moreover, an Analysis is always associated to one or more Experiments and, since the Analysis workflow can be traced back to raw data and its associated analytical samples, the Analysis provides the link between the Experiment and the Sample modules. By default, when a new Analysis is created, it will be assigned to the currently active Experiment. Figure 5 shows the data input window at the Analysis module. The central panel displays the input form for the different analysis steps, while at the bottom a graphical representation of the workflow allows easily monitoring the elements and structure of the Analysis.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig5_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"6f0be8e2024e2fd03250b94100292100\"><img alt=\"Fig5 Hernandez BMCSystemsBiology2014 8-Suppl2.jpg\" src=\"https:\/\/www.limswiki.org\/images\/3\/3d\/Fig5_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 5. Analysis module input window<\/b><\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h2><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Use_case\">Use case<\/span><\/h3>\n<p>To illustrate the usage and functionalities of the STATegra EMS, we consider the registration into the system of a subset of the ENCODE human dataset<sup id=\"rdp-ebb-cite_ref-ENCODEExp_21-0\" class=\"reference\"><a href=\"#cite_note-ENCODEExp-21\" rel=\"external_link\">[21]<\/a><\/sup> comprising the four omics data types (mRNA-seq, ChIP-seq, DNase-seq and Proteomics) of two cell lines GM12878 and K562, with two biological replicates for most data types. ENCODE cell lines were regularly cultured in batches at data production labs to generate the samples for the different sequencing assays. In our example, we consider the utilization of one or several biological replicates from the same batch to obtain the analytical samples for ChIP-seq and proteomics experiments as depicted in Figure 6. An instance of the STATegra EMS with the ENCODE test data fully annotated into the system can be accessed at <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/stategra.eu\/\u200bstategraems_\u200btest\" target=\"_blank\">http:\/\/stategra.eu\/\u200bstategraems_\u200btest<\/a>.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig6_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"53cfea315fa1607f6935293d43bb84d1\"><img alt=\"Fig6 Hernandez BMCSystemsBiology2014 8-Suppl2.jpg\" src=\"https:\/\/www.limswiki.org\/images\/7\/79\/Fig6_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 6. Sample scheme for cell line K562 ENCODE user case data.<\/b> See main text for description.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>At the Experiment Module a new experiment is created by the Experiment owner who assigns registered users to it. The Experiment has a unique ID within the system along with some basic information such as goal, description, type of experiment, experimental design and planned omics measurement types. Check boxes next to each planned measurement are available to monitor the progress of the experiment. These are automatically checked when a matching Analysis is uploaded and assigned to the Experiment. Figure 7 shows the Experiment annotation for our use case: a human-readable name (ENCODE test) and description (STATegra EMS test experiment) are given for the experiment, and the basic experimental details are indicated: multiple conditions experiment type, two biological replicates and three omics types, mRNA-seq, ChIP-seq, DNase-seq and proteomics.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig7_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"887aff86933de7d6093d43896baa133d\"><img alt=\"Fig7 Hernandez BMCSystemsBiology2014 8-Suppl2.jpg\" src=\"https:\/\/www.limswiki.org\/images\/4\/45\/Fig7_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 7. Annotation details at Experiment module.<\/b><\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>Users then fill the Sample Module input form (Figure 8). The first of four sections of this form includes fields for General information on the sample such as sample ID (auto_generated), sample name (K562 or GM12878) and title, which is a more extended description of the sample (Chronic myelogenous leukemia\/Lymphoblastoid). The second section of the form is used to describe the Biomaterial. For this use case, we entered the lymphocyte cell type from the blood tissue in human, with GM12878 as normal and K562 as cancer variation. The Experimental condition section is left blank in this example, since our cell lines did not receive any particular treatment. The next section records the associated Biological Replicates, where we can add items when more than one biological replicate is available for the same biological condition. For this user case, we created nine biological replicates to implement the scheme in Figure 6 and indicated the number for each replicate (i.e. #1), the corresponding batch when applicable, and its derived analytical samples. Analytical samples are characterized by an extraction protocol and a name. Multiple analytical replicates can be created for one biological replicate. For example, the RNA-seq data in our use case has one Analytical sample per each of the two biological replicates obtained with the Caltech long mRNA extraction protocol, while the proteomics data includes four analytical samples corresponding to each sub-cellular fraction (membrane fraction, cytosol, nucleus, mitochondria) (Figure 6).\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig8_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"49fffb33fc621bf745338f0ac3d5699b\"><img alt=\"Fig8 Hernandez BMCSystemsBiology2014 8-Suppl2.jpg\" src=\"https:\/\/www.limswiki.org\/images\/d\/d7\/Fig8_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 8. Sample form.<\/b> The sample form provides fields to annotate biological condition details including data on the associated biological replicates and analytical samples.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>Finally, information about the processing workflows is incorporated in the Analysis module. While the use case involves four omics types, we will only describe the RNA-seq workflow in detail, as the Chip-seq, DNase and Proteomics workflows are conceptually similar.\n<\/p><p>Within the active experiment, a new Analysis is selected, indicating mRNA-seq as the analysis type. Clicking on the \"Annotate new step\" adds each new analysis step. At the beginning of an Analysis \"Raw Data\" is the only option available, which opens the Raw Data form. At this point the user selects an existing Analytical Sample ID to start annotating the library preparation details and sequencing characteristics of a particular sample. In our example, we would choose the Analytical Sample #1 corresponding to Biological Replicate #1 of the K562 cell line. Additionally we can indicate the location of the raw data fastq file in our system. In principle the EMS does not stores any raw or processed data files, and instead provides pointers to the location of these files. Once the Raw Data form is completed and saved, a graphical representation of the analysis workflow is created on the lower screen window of the Analysis Module (Figure 5). This workflow will grow with the subsequent analysis steps. After the Raw Data step is created, additional intermediate steps can be added. In our user case, the next intermediate step to add is the mapping of the reads to the human reference genome, where the user would indicate which raw data file was used and other parameters such a reference genome annotation file or mapping algorithm such as GENCODE hg19 and TopHat respectively. Other subsequent intermediate steps can be envisioned such as trimming, removal of duplicate reads, etc. The analysis workflow ends with a Processed Data step with a form that requires annotation of a previous intermediate or raw data steps. For RNA-seq, one Processed Data step could for example correspond to the Cufflinks gtf file with FPKMs. A completed Analysis can be partially reused and modified to create additional workflows such as one leading to a different Processed Data step. For example, the first two steps of the previous analysis workflow can be imported to create a new workflow having a different Processed Data step recording a junction's bed file obtained by TopHat.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusion\">Conclusion<\/span><\/h2>\n<p>As high-throughput sequencing costs decrease and new sequencing-based molecular assays become available more research laboratories incorporate the NGS technology as a tool to address their scientific goals. This is additionally promoted by the fact that high-throughput sequencing is also feasible in organisms with very little genome information. In a typical scenario, the researcher plans and outsources his\/her experiments to sequencing facilities that might vary over time or according to the specific NGS assay required. When sequencing results arrive and accumulate, a necessity arises to properly store and organize large datasets and their associated processing pipelines. The STATegra EMS has been conceived to provide a management solution in these cases. The architecture of the system was designed having in mind the situation at research labs, where multiple experiments are run, samples might be replicated of reused in successive experiments, and one same biomaterial source could be used for different types of NGS assays. For this, the Sample Module arranges annotation into three Information Units: biological condition, biological replicate and analytical sample allowing one to many relationships, which creates the flexibility to define complex sampling settings without duplication of information. Similarly, the Analysis module divides metadata annotation into steps that can be reused to create alternative analysis workflows. Finally, by allowing samples and analyses to belong to different experiments, the STATegra EMS can accommodate possible connections between experiments.\n<\/p><p>This architecture is substantially different from other solutions created for NGS data that are oriented to sequencing facilities, such as the Galaxy LIMS<sup id=\"rdp-ebb-cite_ref-ScholtalbersGal13_14-1\" class=\"reference\"><a href=\"#cite_note-ScholtalbersGal13-14\" rel=\"external_link\">[14]<\/a><\/sup> which handles requests from users to the service, or the NG6<sup id=\"rdp-ebb-cite_ref-MarietteNG612_13-1\" class=\"reference\"><a href=\"#cite_note-MarietteNG612-13\" rel=\"external_link\">[13]<\/a><\/sup> that controls the sequencing workflow at sequencing providers. In these cases the management system is adapted to the production pipeline at the sequencing center and applies a strong control on the facility wet-lab including library preparation and sequencer runs. This type of information is absent from the STATegra EMS, which may actually accept data from multiple sequencing providers. On the contrary the STATegra EMS records experimental information and sample metadata that might not be relevant at a production center. In conclusion, NGS LIMS and the STATegra EMS target different users and needs in the management of sequencing data. An open challenge is yet to optimize the integration of -<i>seq<\/i> data with clinical information similarly to what is done in clinical development centers.<sup id=\"rdp-ebb-cite_ref-AbugessaisaImp13_22-0\" class=\"reference\"><a href=\"#cite_note-AbugessaisaImp13-22\" rel=\"external_link\">[22]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-AbugessaisaIntND_23-0\" class=\"reference\"><a href=\"#cite_note-AbugessaisaIntND-23\" rel=\"external_link\">[23]<\/a><\/sup>\n<\/p><p>The current STATegra EMS supports analysis workflows for five popular sequencing functional assays but can easily be extended to other *seq applications as processing step forms are generic for DNA and cDNA high-throughput sequencing. Additionally, the system supports annotation of omics experiments targeting non nucleic acid components, such as proteomics and metabolomics for which specific input forms have been incorporated. All together, the STATegra EMS provides an integrated system for annotation of complex high-throughput omics experiments at functional genomics research laboratories.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Availability_and_requirements\">Availability and requirements<\/span><\/h2>\n<p>The STATegra EMS application is distributed under GNU General Public License, Version 3 and can be obtained from <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/stategra.eu\/\u200bstategraems\" target=\"_blank\">http:\/\/stategra.eu\/\u200bstategraems<\/a>. The STATegra EMS was developed in JAVA and is therefore platform independent, but it has only been extensively tested for UNIX environments. The software MySQL server and Apache Tomcat. Installation instructions can be found at <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/stategra.eu\/\u200bstategraems_\u200binstallation\" target=\"_blank\">http:\/\/stategra.eu\/\u200bstategraems_\u200binstallation<\/a>.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Declarations\">Declarations<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h3>\n<p>The authors thank Ali Mortazavi for critical discussion of the manuscript. This work has been funded by the STATegra project, EU FP7 grant number 30600. This work was partially supported by COST-BMBS, Action BM1006 \"Next Generation Sequencing Data Analysis Network\", SeqAhead. The contribution of IA was also supported by \u00c5ke Wibergs Stiftelsen medicine research Diarienr: 719593091 (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ake-wiberg.se\/\u200b\" target=\"_blank\">http:\/\/ake-wiberg.se\/\u200b<\/a>).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Declarations_2\">Declarations<\/span><\/h3>\n<p>The publication costs for this article were funded by the STATegra project, EU FP7 grant number 30600.\n<\/p><p>This article has been published as part of BMC Systems Biology Volume 8 Supplement 2, 2014: Selected articles from the High-Throughput Omics and Data Integration Workshop. The full contents of the supplement are available online at <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.biomedcentral.com\/\u200bbmcsystbiol\/\u200bsupplements\/\u200b8\/\u200bS2\" target=\"_blank\">http:\/\/www.biomedcentral.com\/\u200bbmcsystbiol\/\u200bsupplements\/\u200b8\/\u200bS2<\/a>.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Authors.27_contributions\">Authors' contributions<\/span><\/h3>\n<p>RH conceived, implemented the STATegra EMS and helped drafting the manuscript. NBC helped implementing. IA, DGC and JT helped in conceiving the EMS. AC supervised the work and drafted the manuscript. All authors approved the final version of the manuscript.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Competing_interests\">Competing interests<\/span><\/h3>\n<p>The authors declare no conflicts of interests.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<ol class=\"references\">\n<li id=\"cite_note-SongGenome13-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SongGenome13_1-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Song, C.X.; Szulwach, K.E.; Dai, Q. et al. 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(2001). \"Minimum information about a microarray experiment (MIAME)-toward standards for microarray data\". <i>Nature Genetics<\/i> <b>29<\/b> (4): 365\u2014371. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fng1201-365\" target=\"_blank\">10.1038\/ng1201-365<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/11726920\" target=\"_blank\">11726920<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Minimum+information+about+a+microarray+experiment+%28MIAME%29-toward+standards+for+microarray+data&rft.jtitle=Nature+Genetics&rft.aulast=Brazma%2C+A.%3B+Hingamp%2C+P.%3B+Quackenbush%2C+J.+et+al.&rft.au=Brazma%2C+A.%3B+Hingamp%2C+P.%3B+Quackenbush%2C+J.+et+al.&rft.date=2001&rft.volume=29&rft.issue=4&rft.pages=365%E2%80%94371&rft_id=info:doi\/10.1038%2Fng1201-365&rft_id=info:pmid\/11726920&rfr_id=info:sid\/en.wikipedia.org:Journal:STATegra_EMS:_An_experiment_management_system_for_complex_next-generation_omics_experiments\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-TheFuncMINSEQE12-20\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-TheFuncMINSEQE12_20-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Functional Genomics Data Society. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.fged.org\/projects\/minseqe\/\" target=\"_blank\">\"MINSEQE: Minimum Information about a high throughput Nucleotide SeQuencing Experiment\"<\/a>. <i>fged.org<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.fged.org\/projects\/minseqe\/\" target=\"_blank\">http:\/\/www.fged.org\/projects\/minseqe\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=MINSEQE%3A+Minimum+Information+about+a+high+throughput+Nucleotide+SeQuencing+Experiment&rft.atitle=fged.org&rft.aulast=Functional+Genomics+Data+Society&rft.au=Functional+Genomics+Data+Society&rft_id=http%3A%2F%2Fwww.fged.org%2Fprojects%2Fminseqe%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:STATegra_EMS:_An_experiment_management_system_for_complex_next-generation_omics_experiments\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-ENCODEExp-21\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-ENCODEExp_21-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/genome.ucsc.edu\/ENCODE\/dataMatrix\/encodeDataMatrixHuman.html\" target=\"_blank\">\"ENCODE Experiment Matrix\"<\/a>. UCSC<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/genome.ucsc.edu\/ENCODE\/dataMatrix\/encodeDataMatrixHuman.html\" target=\"_blank\">http:\/\/genome.ucsc.edu\/ENCODE\/dataMatrix\/encodeDataMatrixHuman.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=ENCODE+Experiment+Matrix&rft.atitle=&rft.pub=UCSC&rft_id=http%3A%2F%2Fgenome.ucsc.edu%2FENCODE%2FdataMatrix%2FencodeDataMatrixHuman.html&rfr_id=info:sid\/en.wikipedia.org:Journal:STATegra_EMS:_An_experiment_management_system_for_complex_next-generation_omics_experiments\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-AbugessaisaImp13-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-AbugessaisaImp13_22-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Abugessaisa, I.; Gomez-Cabrero, D.; Snir, O. et al. (2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3623742\" target=\"_blank\">\"Implementation of the CDC translational informatics platform - from genetic variants to the National Swedish Rheumatology Quality Register\"<\/a>. <i>Journal of Translational Medicine<\/i> <b>11<\/b>: 85. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1479-5876-11-85\" target=\"_blank\">10.1186\/1479-5876-11-85<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3623742\/\" target=\"_blank\">PMC3623742<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23548156\" target=\"_blank\">23548156<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3623742\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3623742<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Implementation+of+the+CDC+translational+informatics+platform+-+from+genetic+variants+to+the+National+Swedish+Rheumatology+Quality+Register&rft.jtitle=Journal+of+Translational+Medicine&rft.aulast=Abugessaisa%2C+I.%3B+Gomez-Cabrero%2C+D.%3B+Snir%2C+O.+et+al.&rft.au=Abugessaisa%2C+I.%3B+Gomez-Cabrero%2C+D.%3B+Snir%2C+O.+et+al.&rft.date=2013&rft.volume=11&rft.pages=85&rft_id=info:doi\/10.1186%2F1479-5876-11-85&rft_id=info:pmc\/PMC3623742&rft_id=info:pmid\/23548156&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC3623742&rfr_id=info:sid\/en.wikipedia.org:Journal:STATegra_EMS:_An_experiment_management_system_for_complex_next-generation_omics_experiments\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-AbugessaisaIntND-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-AbugessaisaIntND_23-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Abugessaisa, I.; Saevarsdottir, S.; Tsipras, G. et al.. \"Integrating Clinically Driven Development with suitable Database Architecture in Assembling an Informatics Fusion Platform to Accelerate Translational Research\". <i>(Submitted to) Science Translational Medicine<\/i>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Integrating+Clinically+Driven+Development+with+suitable+Database+Architecture+in+Assembling+an+Informatics+Fusion+Platform+to+Accelerate+Translational+Research&rft.jtitle=%28Submitted+to%29+Science+Translational+Medicine&rft.aulast=Abugessaisa%2C+I.%3B+Saevarsdottir%2C+S.%3B+Tsipras%2C+G.+et+al.&rft.au=Abugessaisa%2C+I.%3B+Saevarsdottir%2C+S.%3B+Tsipras%2C+G.+et+al.&rfr_id=info:sid\/en.wikipedia.org:Journal:STATegra_EMS:_An_experiment_management_system_for_complex_next-generation_omics_experiments\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. References 17 and 18 were not attached to any text in the original, so author names were added to the text for better flow.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192205\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.647 seconds\nReal time usage: 0.686 seconds\nPreprocessor visited node count: 19665\/1000000\nPreprocessor generated node count: 32755\/1000000\nPost\u2010expand include size: 174799\/2097152 bytes\nTemplate argument size: 56706\/2097152 bytes\nHighest expansion depth: 18\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 629.454 1 - -total\n 85.79% 539.985 1 - Template:Reflist\n 75.76% 476.881 23 - Template:Citation\/core\n 73.43% 462.218 21 - Template:Cite_journal\n 10.75% 67.690 49 - Template:Citation\/identifier\n 9.88% 62.177 1 - Template:Infobox_journal_article\n 9.47% 59.637 1 - Template:Infobox\n 6.45% 40.614 2 - Template:Cite_web\n 5.74% 36.123 80 - Template:Infobox\/row\n 4.63% 29.155 24 - Template:Citation\/make_link\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:8465-0!*!0!!en!5!* and timestamp 20181214192205 and revision id 24757\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:STATegra_EMS:_An_experiment_management_system_for_complex_next-generation_omics_experiments\">https:\/\/www.limswiki.org\/index.php\/Journal:STATegra_EMS:_An_experiment_management_system_for_complex_next-generation_omics_experiments<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","b8605708462c7083aa1f73a384e9fe8c_images":["https:\/\/www.limswiki.org\/images\/c\/c9\/Fig1_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg","https:\/\/www.limswiki.org\/images\/b\/b4\/Fig2_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg","https:\/\/www.limswiki.org\/images\/3\/3c\/Fig3_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg","https:\/\/www.limswiki.org\/images\/5\/5f\/Fig4_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg","https:\/\/www.limswiki.org\/images\/3\/3d\/Fig5_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg","https:\/\/www.limswiki.org\/images\/7\/79\/Fig6_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg","https:\/\/www.limswiki.org\/images\/4\/45\/Fig7_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg","https:\/\/www.limswiki.org\/images\/d\/d7\/Fig8_Hernandez_BMCSystemsBiology2014_8-Suppl2.jpg"],"b8605708462c7083aa1f73a384e9fe8c_timestamp":1544815325,"ee17c209b3c5cfdc21c7923559a9a449_type":"article","ee17c209b3c5cfdc21c7923559a9a449_title":"OpenChrom: A cross-platform open source software for the mass spectrometric analysis of chromatographic data (Wenig et al. 2010)","ee17c209b3c5cfdc21c7923559a9a449_url":"https:\/\/www.limswiki.org\/index.php\/Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data","ee17c209b3c5cfdc21c7923559a9a449_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:OpenChrom: A cross-platform open source software for the mass spectrometric analysis of chromatographic data\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nOpenChrom: A cross-platform open source software for the mass spectrometric analysis of chromatographic dataJournal\n \nBMC BioinformaticsAuthor(s)\n \nWenig, Philip; Odermatt, JuergenAuthor affiliation(s)\n \nUniversity of HamburgPrimary contact\n \nEmail: philip.wenig@gmx.netYear published\n \n2010Volume and issue\n \n11Page(s)\n \n405DOI\n \n10.1186\/1471-2105-11-405ISSN\n \n1471-2105Distribution license\n \nCreative Commons Attribution 2.0 GenericWebsite\n \nhttp:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-11-405Download\n \nhttp:\/\/bmcbioinformatics.biomedcentral.com\/track\/pdf\/10.1186\/1471-2105-11-405 (PDF)\n\nContents\n\n1 Abstract \n\n1.1 Background \n1.2 Results \n1.3 Conclusions \n\n\n2 Background \n\n2.1 Implementation \n\n2.1.1 Architecture \n2.1.2 Object model \n2.1.3 Extension points \n2.1.4 Graphical user interface \n\n\n\n\n3 Results and discussion \n4 Conclusions \n5 Availability and requirements \n6 Declarations \n\n6.1 Acknowledgements \n6.2 Authors\u2019 original submitted files for images \n6.3 Authors' contributions \n\n\n7 References \n8 Notes \n\n\n\nAbstract \nBackground \nToday, data evaluation has become a bottleneck in chromatographic science. Analytical instruments equipped with automated samplers yield large amounts of measurement data, which needs to be verified and analyzed. Since nearly every GC\/MS instrument vendor offers its own data format and software tools, the consequences are problems with data exchange and a lack of comparability between the analytical results. To challenge this situation a number of either commercial or non-profit software applications have been developed. These applications provide functionalities to import and analyze several data formats but have shortcomings in terms of the transparency of the implemented analytical algorithms and\/or are restricted to a specific computer platform.\n\nResults \nThis work describes a native approach to handle chromatographic data files. The approach can be extended in its functionality such as facilities to detect baselines, to detect, integrate and identify peaks and to compare mass spectra, as well as the ability to internationalize the application. Additionally, filters can be applied on the chromatographic data to enhance its quality, for example to remove background and noise. Extended operations like do, undo and redo are supported.\n\nConclusions \nOpenChrom is a chromatography software application to edit and analyze mass spectrometric chromatographic data. It is extensible in many different ways, depending on the demands of the users or the analytical procedures and algorithms. It offers a customizable graphical user interface. The software is independent of the operating system, due to the fact that the Rich Client Platform is written in Java. OpenChrom is released under the Eclipse Public License 1.0 (EPL). There are no license constraints regarding extensions. They can be published using open source as well as proprietary licenses. OpenChrom is available free of charge at http:\/\/www.openchrom.net.\n\nBackground \nSoftware has become an integral part of analysis techniques. Especially in the area of gas chromatography\/mass spectrometry, automatic samplers enable high throughput analyses. Software assists handling large amounts of data generated by automated and fast operating analytical instruments. Modern computer systems are inexpensive, powerful and allow analysis techniques that could not have been applied in the past. Deconvolution, a chromatographic quality enhancing technique, demonstrates for instance that increasing processor power makes new analysis techniques applicable. The technique of deconvolution has been described by Biller and Biemann[1][2], Dromey et al.[3], Colby[4], Hindmarch et al.[5], Halket et al.[6], Kong et al.[7], Taylor et al.[8], Pool et al.[9][10] and Davies[11] in various ways. Stein[12] published an enhanced deconvolution algorithm that has been implemented in the software AMDIS (Automated Mass Spectral Deconvolution and Identification System).[13] AMDIS is available free of charge from the National Institute of Standards and Technology (NIST). Windig et al.[14][15] described another approach to enhance chromatographic quality by a deconvolution method called CODA (Component Detection Algorithm). The commercially available software ACD\/MS Manager[16] offers an implementation of this approach.\nIncreasing computational power enables new applications, but there is still a lack of interoperability. Instrument vendors, such as Agilent Technologies, Shimadzu, Thermo Fisher Scientific and Waters Corporation have created their own software and data format. Usually, the mass spectral data formats are binary and can only be accessed by the instrument vendors' proprietary software. Some commercial tools exist to convert the mass spectral data files into other formats, such as MASS Transit from PALISADE Corporation.[17] To avoid these limitations, some efforts have been made to design and implement interoperable data formats and software libraries as for example NetCDF[18] or mzXML.[19][20] But even if it is possible to convert the data files to other formats, there are drawbacks in data processing as each software implements specific functions, has its own graphical user interface and is in most cases commercially available only, as for example the applicable software of ChemStation, Xcalibur or MassLynx. Hence, the users are forced to become familiar with different software systems, user interfaces and methods. Moreover, the software tools primarily target only specific operating systems, such as Microsoft Windows and Mac OSX. The number of software applications that are independent of the operating system and can also be run under Unix or Linux is limited. Linux systems are open source, available at no cost and their usage increases in scientific research (see Scientific Linux[21]), as well as in the public sector.[22][23] Software applications, such as AMDIS, have been published to be used free of charge, but their source code is not disposable. Thus, it is not possible to evaluate the algorithms implemented in the software. Especially in the case of scientific research, it is not possible to figure them out and to extend them. Even if algorithms are described in published papers[2][4][9][12][24], it is often impossible to validate them manually due to the complexity of chromatographic data. Other applications like ChemStation, Xcalibur, and ACD\/MS Manager are proprietary and closed source. They are only commercially available. There is no means of revealing the correctness of their utilized algorithms. Efforts have been made to solve the problems of missing interoperability and restricted access to source codes and algorithms.[25] Bioclipse is a sophisticated project that is open source and is focused with its algorithms on metabolism analysis and gene sequencing. Its techniques are state-of-the-art. Some other projects are mMass[26], COMSPARI[27] and fityk[28], but they do have some restrictions regarding their interoperability and extensibility. BioSunMS[29] is a tool to read TOF (Time of Flight) mass spectral data files, but it is not able to read instrument vendors' native data files. The Chemistry Development Kit (CDK)[30] implements convenient features to edit chemical data and structures, but it has no appropriate user interface. The open source tool OpenMS[31] aims to edit mass spectrometric data, but it is not completely platform independent, as it is written in C++ programming language.\nProjects like Bioclipse, Sashimi[32] or TPP (Trans-Proteomic Pipeline)[33] are focused on the evaluation of metabolism products and gene sequencing and make extensive use of accurate mass resolution techniques. But there is still a lack of software systems that are capable to enhance nominal mass spectral data files, that are flexible, extensible and that offer an easy to use graphical user interface. According to the authors' knowledge, no application offers functions to import vendor systems chromatographic data files and has the ability to edit and analyze chromatograms in the way ChemStation and AMDIS do. No application combines the flexibility in analyses, is easily extensible, open source, platform independent and has a configurable graphical user interface.\n\nImplementation \nArchitecture \nOpenChrom is an open source software that aims to solve the aforementioned constraints getting rid of several restrictions. It is based on the Eclipse Rich Client Platform (RCP)[34], which is an OSGi (Open Service Gateway Initiative) based application environment that allows to build modular and flexible software systems. With the OSGi platform it is possible to extend the functionality of an application by dividing its components into different bundles. It is written in Java which is an interpreted language that depends on the Java Virtual Machine (JVM) and allows the execution of the software on several operating systems (Microsoft Windows, Mac OSX, Unix, Linux) and processor platforms (x86, PPC, AMD64, IA64, SPARC). It utilizes SWT (Standard Widget Toolkit) to render its graphical user interface by using the native resources of the underlying operating system. The Rich Client Platform is state-of-the-art in today's software development. The platform is open to be extended afterwards due to the chosen concepts. It means that the platform doesn't need to be full-fledged at the beginning. Further methods and implementations can be developed separately. Nonetheless, still some effort is necessary to design a platform that covers all needs of a software application to edit, evaluate and modify chromatographic data. In contrast to Bioclipse, Sashimi or TPP, OpenChrom has a slightly different scope, as it is focused primarily on nominal mass resolution data. Mass spectrometers for nominal mass resolution are inexpensive, as for example quadrupole or ion trap instruments. But the data acquisition limits the range of possible applications. Software has the potential to enhance the quality of the recorded data, in contrary to the given limitations. Hence, the Rich Client Platform and the Java programming language were chosen, as they offer an excellent support for a highly extensible and abstract base framework. The OSGi based Rich Client Platform Equinox supports the definition of extension points. The use of different class paths makes it possible to execute code from separated bundles (Figure 1). New functionality, e.g. to export a given chromatogram to a PDF file, can be implemented in a separate bundle making use of the extension point mechanism to import and export chromatographic data.\n\n\n\n\n\n\n\n\n\n Figure 1. RCP\/OSGi and OpenChrom architecture. The RCP\/OSGi and OpenChrom architecture shows the supported processor platforms and operating systems.\n\n\n\nTools in different areas have been implemented based on the Rich Client Platform, such as the Eclipse IDE (Integrated Development Environment), Lotus Notes, Bioclipse, BioSunMS, XMind, Apache Directory Studio and several more. It is part of the OpenChrom architecture to define useful extension points and to build a suitable object model.\n\nObject model \nOpenChrom provides a designed object model to define chromatograms, scans, mass spectra, peaks and baselines. It is important to abstract the base model, as it reduces dependencies in code and allows for the implemention of further extensions. Therefore, the decision was to support an enhanced chromatogram, mass spectrum and peak model, written in Java. There is no preliminary compilation necessary on different operating systems. Further on, it is possible to cover special needs regarding the import of instrument vendors' binary chromatographic files. An excerpt of the OpenChrom object model is shown in a simplified UML (Unified Modeling Language) diagram (Figure 2). Java, as an object orientated language, supports the use of the four base strategies in object orientation: abstraction, encapsulation, polymorphic behavior and inheritance.[35] OpenChrom makes extensive use of the object orientated concept. The interface \"IChromatogram\" and the abstract class \"AbstractChromatogram\" define and implement methods, which are common for all types of chromatograms, independent of the instrument vendors' data format. Therefore, it is not necessary to implement them iterative in each vendor specific chromatogram class. The base framework and extension points, like peak detectors and integrators, are working still with instances of the type \"IChromatogram\", instead of taking for example the differences of an Agilent and a NetCDF chromatogram into account. The object model for mass spectra and mass fragments, peaks and baselines is implemented in a similar way.\n\n\n\n\n\n\n\n\n\n Figure 2. OpenChrom chromatogram object model. The OpenChrom chromatogram object model shows a simplified UML diagram of the chromatographic model OpenChrom uses.\n\n\n\nExtension points \nThe OpenChrom framework offers several bundles (Table 1). The most important one defines methods to implement specialized bundles that handle the import of chromatographic mass spectral data. It is possible to supply a bundle that is able to read binary chromatogram files, given by a specific instrument vendor. The bundle takes care of how to read a given file or directory. Furthermore, the framework offers extension points to detect and integrate peaks. The peak detection and integration have been separated, to make it possible to detect peaks with several peak detector methods and to integrate them with a specified integrator. This results in a more complex but also more flexible system. There is another extension point that allows to define bundles that are capable of detecting a baseline in the chromatogram model. Another flexible extension point was introduced, called filters. Bundles can extend the filter extension point to achieve a quality enhancement of the chromatographic data. They work comparable to filters in image processing software. One filter extension can for instance offer a set of methods to eliminate background signals from the chromatogram. Another filter can implement a routine to mean normalize the chromatogram. The filters offer editing steps, which are especially useful before peak detection and integration routines.\n\n\n\n\n\n\n\nTable 1. Some selected bundles of the OpenChrom software. The OpenChrom software offers several extension points. Extension points are declared in bundles. The table shows a selected overview of bundles and suppliers.\n\n\nBundle\n\nDescription\n\n\nbaseline.detector\n\nDetect baselines\n\n\ncomparison\n\nCompare chromatograms and mass spectra\n\n\nconverter\n\nConverter to read binary\/textual data files\n\n\nconverter.supplier.agilent\n\nRead Agilent data files\n\n\nconverter.supplier.cdf\n\nRead and write NetCDF data files\n\n\nfilter\n\nModify chromatographic data\n\n\nidentifier\n\nIdentify chromatograms, mass spectra and peaks\n\n\nintegrator\n\nIntegrate peaks\n\n\nmodel\n\nModels (chromatogram, mass spectrum, peak,...)\n\n\npeak.detector\n\nDetect peaks\n\n\nlogging\n\nLogging facility\n\n\nrcp\n\nBase application\n\n\nthirdpartylibraries.*\n\nThird party libraries (SWTChart, log4j,...)\n\n\n\nGraphical user interface \nThe Rich Client Platform offers a wide support to present an appropriate graphical user interface. Concepts detailing this include editors, views, perspectives, wizards, menus, cheat sheets, settings and help pages. OpenChrom makes extensive use of the available concepts. The editor shows the graphical representation of a chromatogram and several options, as for example a page to select or exclude distinct mass fragments. It also supports functions to save, edit and analyze chromatograms. The views are used to show different aspects of the chromatographic model. It is possible to show peaks in different kind of views. One view could show a peak including the background of the chromatogram. Another could show the peak with its increasing and decreasing tangents and its width at 50% height. A flexible mechanism was introduced to inform all views if the chromatogram selection has been changed. The update functionality is also realized by an extension point. Views and editors are composed in a task specific way using perspectives.\n\nResults and discussion \nThe OpenChrom software offers several options to edit and evaluate chromatographic data. It currently implements native converters to import mass spectrometric chromatograms from Agilent Technologies and to import and export NetCDF and mzXML files as well as a custom XML format to store the chromatographic data and additional information. The chromatogram file explorer (Figure 3) shows a representation of the local file system and marks those files and directories that contain importable chromatographic data files or directories. The chromatogram can either be stored in a file, a directory or a set of files, as the converter extension point and the import and export converters take care of it. The chromatogram will be opened by a double click on the file. Additionally, a preview of the selected chromatogram file is shown in a specialized view in the user interface. The chromatogram itself is shown in a multi-page editor that is divided into a chromatogram as well as an options page. It is possible to save the chromatogram in several file formats. The NetCDF, mzXML and the customized OpenChrom XML format are actually supported. Nonetheless, the time to import and to save a chromatogram depends on its format and size. It takes more time to process XML based formats like mzXML than binary formats like NetCDF or Agilents data format. The graphical elements are drawn using SWTChart and SWT. Chromatogram selections can be chosen by applying a \"zoom in\" or \"zoom out\" action in the chromatogram editor. All views will be updated after a zoom action.\n\n\n\n\n\n\n\n\n\n Figure 3. OpenChrom software showing editors, views, menus and menu entries. The OpenChrom software is using editors, views, menus and menu entries showed in the figure.\n\n\n\nThe menu \"Chromatogram Edit\" allows to access functions that modify or evaluate the chromatographic data. For example, all registered bundles that support filters will be listed in the sub menu \"Filter\". It is possible to add a filter that implements a Savitzky-Golay[36] smoothing operation or to add filters that remove the background of the chromatogram. Each action will be performed on the active chromatogram selection. Actions are commonly very fast, due to the fact that the chromatogram is kept in the random access memory (RAM), depending on the implemented algorithms. Furthermore, the filter actions are reversible. This editing support is well known from modern IDEs and office suites. But the support for do\/undo and redo operations does cost processing time. If the reversibility is not needed, it can be deactivated in the applications preference dialog. Another extension point is responsible to register baseline detectors. Different baseline detectors can be implemented in separated bundles and will be offered in the \"Baseline Detectors\" sub menu. Peak detection and integration are done commonly in one run. One improvement achieved through OpenChrom is a division of the detection and the integration of peaks into two separated actions. The peak detectors can be applied by calling an appropriate detector in the sub menu \"Peak Detectors\" and the peak integration can be performed by using an listed integrator from the sub menu \"Integrators\". The separation of detector and integrator methods makes it possible to detect peaks in a chromatogram using several algorithms and methods. The chosen peak detectors could be of different types, as for example detectors using deconvolution techniques like AMDIS or CODA. All detected peaks can afterwards be integrated by a unique integrator, which leads to comparable results. This feature offers a high flexibility in using different kinds of detectors and integrators.\nThe view mechanism of the Eclipse Rich Client Platform makes it possible to show chromatographic data in different kind of views. A peak can be displayed in multiple ways, for example by its area (Figure 4), its increasing and decreasing tangents and its width at 50% of peak height. Thus, the system provides additional graphical information, especially useful for educational purposes. Each view can be shown in a small (Figure 3) and extended format (Figure 4 and 5), which allows an appropriate user interaction even on small displays.\n\n\n\n\n\n\n\n\n\n Figure 4. Peak with increasing and decreasing tangents and its width at 50% height in extended format. The view shows a maximized version of a selected peak.\n\n\n\n\n\n\n\n\n\n\n\n\n Figure 5. Graphical representation of a mass spectrum in extended format. The view shows a maximized version of a selected mass spectrum.\n\n\n\nFurther on, property views show miscellaneous values of the selected chromatogram. Due to the chromatogram object model, different values will be shown if different chromatogram files have been loaded. Chromatograms from Agilent Technologies and NetCDF differ in their information content. Hence, the properties view helps to inspect the files. There are additional extension points implemented that enable adding bundles to compare mass spectra using different methods[24][37][38][39][40] or to identify peaks or chromatograms. A method similar to the one implemented in the software F-Search[41] from Frontier Laboratories Ltd. could be used to identify chromatograms, for example.\nMoreover, the OpenChrom platform supports bundles with a system built-in logging mechanism that extends the Apache project log4j. Each module can use the logging mechanism which makes it easier to detect problems and failures. Bundles are further separated into fragments, which allows the separation of concerns. Each OpenChrom bundle supports an internationalization (i18n) and JUnit test fragment. At the moment, approximately 3000 unit tests are written and can be executed to ensure the quality of the software.\nIf necessary, the extension point mechanism gives the flexibility to add functions needed by users at any time. Thus, OpenChrom can be connected to other systems, as for example to LIMS (Laboratory Information Management System), databases, existing software tools or workflow systems. The object model of OpenChrom offers a convenient access to values and results from the edited chromatograms. Specialized modules take care of how to handle specific concerns, for example how to store results in an information management system. Further on, it is possible to implement bundles for specific analyses or for an automated experimentation.\nOpenChrom enables several ways to edit and analyze chromatographic data. The advantage of the flexibility and the abstract architecture makes it partly difficult to get started with the platform, even if the functionality is provided by different bundles to decrease its complexity and to focus on special tasks. The intention to publish the software under an open source license is to support code contributions and to open the project for individual solutions. Moreover, the separation into bundles makes it easier for others to contribute new functionality. Further improvements will be done to optimize the current algorithms and to develop new and better filters, peak detectors and integrators.\n\nConclusions \nOpenChrom has been designed to become an extensible cross-platform open source software for the mass spectrometric analysis of chromatographic data. It provides extension points to enable built-in import capabilities for binary or textual instrument vendors' data formats. In addition to its custom XML format it supports the Agilent Technologies, mzXML and NetCDF mass spectrometric data format. Further development is planned to support more data formats. The open source concept has been chosen to initiate the contributions of third parties, as it depends on the ideas and needs of the community to extend the capabilities of the presented concept. OpenChrom offers extension points that enable the implementation of different baseline detectors as well as peak detectors and integrators. Furthermore, there is an option to implement filters, used to increase the chromatographic quality. The framework offers a full support of do\/undo and redo operations. The examples Bioclipse and BioSunMS show how to use the Eclipse Rich Client Platform in a specific way, but no software has been published until now that is capable to import binary chromatographic files natively, offers support to edit and analyze chromatograms and makes it possible to implement new algorithms and methods. As it is open source, everybody has the possibility to inspect the implemented algorithms and methods, especially for verification. OpenChrom is a software with a special focus on the editing and evaluation of mass spectrometric chromatographic data. OpenChrom will be hopefully extended by contributing developers, scientists and companies in the future.\n\nAvailability and requirements \nProject name: OpenChrom\nProject homepage: http:\/\/\u200bwww.\u200bopenchrom.\u200bnet\nOperating systems: Platform independent\nProgramming language: Java\nJava Runtime Environment: Sun\/Oracle JVM 1.6.0, OpenJDK\nMinimum RAM: 500 MB\nMinimum Processor: 1 GHz\nCommercial restrictions: None\nOpenChrom is available for download free of charge from the project home page.\nThe Agilent data file input converter must be installed separately using the OpenChrom update mechanism. The instructions how to install the converter can be found at the following website: https:\/\/marketplace.openchrom.net\/.\nOpenChrom is licensed under the Eclipse Public License 1.0 (EPL). The EPL is an OSI approved open source license that ensures, that the source code will remain open source. OpenChrom uses some third party libraries that are partly published under different open source licenses. All third party libraries are available in separated bundles, to ensure that no license conflicts occur. The third party library bundles are published under the Apache, LGPL, AGPL and EPL license, depending on the bundle. The GPL licenses are viral, it means that derivative works must be published under the GPL license too. The EPL and Eclipse Rich Client Platform enable a different licensing for the bundles, as a bundle using methods of another bundle can not be seen as a derivative work, though it only uses its interfaces.\n\nDeclarations \nAcknowledgements \nThe authors thank all participants at the Department of Wood Science (University of Hamburg, Germany) for their support and their helpful suggestions.\n\nAuthors\u2019 original submitted files for images \nBelow are the links to the authors\u2019 original submitted files for images.\n\n 12859_2010_3862_MOESM1_ESM.png Authors\u2019 original file for figure 1\n 12859_2010_3862_MOESM2_ESM.png Authors\u2019 original file for figure 2\n 12859_2010_3862_MOESM3_ESM.png Authors\u2019 original file for figure 3\n 12859_2010_3862_MOESM4_ESM.png Authors\u2019 original file for figure 4\n 12859_2010_3862_MOESM5_ESM.png Authors\u2019 original file for figure 5\nAuthors' contributions \nPW designed and implemented the core API (Application Programming Interface), the software and its extension points. PW drafted most of the manuscript. JO gave feedback and corrected the manuscript. All authors performed extensive testing of the software and approved the final manuscript.\n\nReferences \n\n\n\u2191 Biller, J.E.; Herlihy, W.C.; Biemann, K. (1977). \"Identification of the components of complex mixtures by GC-MS\". Abstracts Of Papers Of The American Chemical Society 173 (MAR20): 23\u201323. http:\/\/pubs.acs.org\/doi\/abs\/10.1021\/bk-1977-0054.ch002 .   \n\n\u2191 2.0 2.1 Biller, J.E.; Biemann, K. (1974). \"Reconstructed Mass Spectra, A Novel Approach for the Utilization of Gas Chromatograph\u2014Mass Spectrometer Data\". Analytical Letters 7 (7): 515\u2013528. doi:10.1080\/00032717408058783.   \n\n\u2191 Dromey, R.G.; Stefik, M.J.; Rindfleisch, T.C.; Duffield, A.M. (1976). \"Extraction of mass spectra free of background and neighboring component contributions from gas chromatography\/mass spectrometry data\". 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(1998). \"Comparison of algorithms and databases for matching unknown mass spectra\". Journal of the American Society for Mass Spectrometry 9 (1): 92-95. doi:10.1016\/S1044-0305(97)00235-3. PMID 9679594.   \n\n\u2191 Loh, S.Y.; McLafferty, F.W. (1991). \"Exact mass probability based matching of high-resolution unknown mass spectra\". Analytical Chemistry 63 (6): 546\u2013550. doi:10.1021\/ac00006a002.   \n\n\u2191 Damen, H.; Henneberg, D.; Weimann, B. (1978). \"Siscom \u2014 a new library search system for mass spectra\". Analytica Chimica Acta 103 (4): 289-302. doi:10.1016\/S0003-2670(01)83095-6.   \n\n\u2191 Alfassi, Z.B. (2005). \"Vector analysis of multi-measurements identification\". Journal of Radioanalytical and Nuclear Chemistry 266 (2): 245\u2013250. doi:10.1007\/s10967-005-0899-y.   \n\n\u2191 \"Frontier Lab\". Frontier Laboratories Ltd. http:\/\/www.frontier-lab.com\/ .   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. In the \"Conclusion\" section of the abstract, \"software\" was changed to \"chromatography software\" to encourage internal linking to the CDMS entry on the wiki. Two blank rows were removed from Table 1. A few URLS have changed since this was published in 2010, and they have been updated as needed.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\">https:\/\/www.limswiki.org\/index.php\/Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on chromatographyLIMSwiki journal articles on software\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 26 March 2016, at 16:27.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 1,919 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","ee17c209b3c5cfdc21c7923559a9a449_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_OpenChrom_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:OpenChrom: A cross-platform open source software for the mass spectrometric analysis of chromatographic data<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Background\">Background<\/span><\/h3>\n<p>Today, data evaluation has become a bottleneck in <a href=\"https:\/\/www.limswiki.org\/index.php\/Chromatography\" title=\"Chromatography\" target=\"_blank\" class=\"wiki-link\" data-key=\"2615535d1f14c6cffdfad7285999ad9d\">chromatographic science<\/a>. Analytical instruments equipped with automated samplers yield large amounts of measurement data, which needs to be verified and analyzed. Since nearly every <a href=\"https:\/\/www.limswiki.org\/index.php\/Gas_chromatography%E2%80%93mass_spectrometry\" title=\"Gas chromatography\u2013mass spectrometry\" target=\"_blank\" class=\"wiki-link\" data-key=\"d7fe02050f81fca3ad7a5845b1879ae2\">GC\/MS<\/a> instrument vendor offers its own data format and software tools, the consequences are problems with data exchange and a lack of comparability between the analytical results. To challenge this situation a number of either commercial or non-profit software applications have been developed. These applications provide functionalities to import and analyze several data formats but have shortcomings in terms of the transparency of the implemented analytical algorithms and\/or are restricted to a specific computer platform.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h3>\n<p>This work describes a native approach to handle chromatographic data files. The approach can be extended in its functionality such as facilities to detect baselines, to detect, integrate and identify peaks and to compare mass spectra, as well as the ability to internationalize the application. Additionally, filters can be applied on the chromatographic data to enhance its quality, for example to remove background and noise. Extended operations like do, undo and redo are supported.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h3>\n<p><a href=\"https:\/\/www.limswiki.org\/index.php\/OpenChrom\" title=\"OpenChrom\" target=\"_blank\" class=\"wiki-link\" data-key=\"586c3f92f680ab8c89b40007151a28e7\">OpenChrom<\/a> is a <a href=\"https:\/\/www.limswiki.org\/index.php\/Chromatography_data_management_system\" title=\"Chromatography data management system\" target=\"_blank\" class=\"wiki-link\" data-key=\"e0b59eaaca214b3b757b613af60743ad\">chromatography software<\/a> application to edit and analyze mass spectrometric chromatographic data. It is extensible in many different ways, depending on the demands of the users or the analytical procedures and algorithms. It offers a customizable graphical user interface. The software is independent of the operating system, due to the fact that the Rich Client Platform is written in Java. OpenChrom is released under the Eclipse Public License 1.0 (EPL). There are no license constraints regarding extensions. They can be published using open source as well as proprietary licenses. OpenChrom is available free of charge at <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.openchrom.net\" target=\"_blank\">http:\/\/www.openchrom.net<\/a>.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Background_2\">Background<\/span><\/h2>\n<p>Software has become an integral part of analysis techniques. Especially in the area of gas chromatography\/mass spectrometry, automatic samplers enable high throughput analyses. Software assists handling large amounts of data generated by automated and fast operating analytical instruments. Modern computer systems are inexpensive, powerful and allow analysis techniques that could not have been applied in the past. Deconvolution, a chromatographic quality enhancing technique, demonstrates for instance that increasing processor power makes new analysis techniques applicable. The technique of deconvolution has been described by Biller and Biemann<sup id=\"rdp-ebb-cite_ref-BillerIdent77_1-0\" class=\"reference\"><a href=\"#cite_note-BillerIdent77-1\" rel=\"external_link\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-BillerRecon74_2-0\" class=\"reference\"><a href=\"#cite_note-BillerRecon74-2\" rel=\"external_link\">[2]<\/a><\/sup>, Dromey et al.<sup id=\"rdp-ebb-cite_ref-FromeyExtract76_3-0\" class=\"reference\"><a href=\"#cite_note-FromeyExtract76-3\" rel=\"external_link\">[3]<\/a><\/sup>, Colby<sup id=\"rdp-ebb-cite_ref-ColbySpect92_4-0\" class=\"reference\"><a href=\"#cite_note-ColbySpect92-4\" rel=\"external_link\">[4]<\/a><\/sup>, Hindmarch et al.<sup id=\"rdp-ebb-cite_ref-HindmarchDecon96_5-0\" class=\"reference\"><a href=\"#cite_note-HindmarchDecon96-5\" rel=\"external_link\">[5]<\/a><\/sup>, Halket et al.<sup id=\"rdp-ebb-cite_ref-HalketDecon99_6-0\" class=\"reference\"><a href=\"#cite_note-HalketDecon99-6\" rel=\"external_link\">[6]<\/a><\/sup>, Kong et al.<sup id=\"rdp-ebb-cite_ref-KongDecon05_7-0\" class=\"reference\"><a href=\"#cite_note-KongDecon05-7\" rel=\"external_link\">[7]<\/a><\/sup>, Taylor et al.<sup id=\"rdp-ebb-cite_ref-TaylorTheDecon98_8-0\" class=\"reference\"><a href=\"#cite_note-TaylorTheDecon98-8\" rel=\"external_link\">[8]<\/a><\/sup>, Pool et al.<sup id=\"rdp-ebb-cite_ref-PoolBack96_9-0\" class=\"reference\"><a href=\"#cite_note-PoolBack96-9\" rel=\"external_link\">[9]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-PoolAuto97_10-0\" class=\"reference\"><a href=\"#cite_note-PoolAuto97-10\" rel=\"external_link\">[10]<\/a><\/sup> and Davies<sup id=\"rdp-ebb-cite_ref-DaviesTheNew98_11-0\" class=\"reference\"><a href=\"#cite_note-DaviesTheNew98-11\" rel=\"external_link\">[11]<\/a><\/sup> in various ways. Stein<sup id=\"rdp-ebb-cite_ref-SteinAnInt99_12-0\" class=\"reference\"><a href=\"#cite_note-SteinAnInt99-12\" rel=\"external_link\">[12]<\/a><\/sup> published an enhanced deconvolution algorithm that has been implemented in the software AMDIS (Automated Mass Spectral Deconvolution and Identification System).<sup id=\"rdp-ebb-cite_ref-AMDIS_13-0\" class=\"reference\"><a href=\"#cite_note-AMDIS-13\" rel=\"external_link\">[13]<\/a><\/sup> AMDIS is available free of charge from the National Institute of Standards and Technology (NIST). Windig et al.<sup id=\"rdp-ebb-cite_ref-WindigChemo07_14-0\" class=\"reference\"><a href=\"#cite_note-WindigChemo07-14\" rel=\"external_link\">[14]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-WindigANoise96_15-0\" class=\"reference\"><a href=\"#cite_note-WindigANoise96-15\" rel=\"external_link\">[15]<\/a><\/sup> described another approach to enhance chromatographic quality by a deconvolution method called CODA (Component Detection Algorithm). The commercially available software ACD\/MS Manager<sup id=\"rdp-ebb-cite_ref-ACD.2FMS_16-0\" class=\"reference\"><a href=\"#cite_note-ACD.2FMS-16\" rel=\"external_link\">[16]<\/a><\/sup> offers an implementation of this approach.\n<\/p><p>Increasing computational power enables new applications, but there is still a lack of interoperability. Instrument vendors, such as <a href=\"https:\/\/www.limswiki.org\/index.php\/Agilent_Technologies,_Inc.\" title=\"Agilent Technologies, Inc.\" target=\"_blank\" class=\"wiki-link\" data-key=\"dcea1a676a012bcbe3af9562dd17f8a0\">Agilent Technologies<\/a>, <a href=\"https:\/\/www.limswiki.org\/index.php\/Shimadzu_Corporation\" title=\"Shimadzu Corporation\" target=\"_blank\" class=\"wiki-link\" data-key=\"b55dff14f2cd33d62456eb1653d4cad5\">Shimadzu<\/a>, <a href=\"https:\/\/www.limswiki.org\/index.php\/Thermo_Scientific\" title=\"Thermo Scientific\" target=\"_blank\" class=\"wiki-link\" data-key=\"e914753f99d483d4577b35fed71b3c94\">Thermo Fisher Scientific<\/a> and <a href=\"https:\/\/www.limswiki.org\/index.php\/Waters_Corporation\" title=\"Waters Corporation\" target=\"_blank\" class=\"wiki-link\" data-key=\"d17153eab93be07066660e3cff4b84c5\">Waters Corporation<\/a> have created their own software and data format. Usually, the mass spectral data formats are binary and can only be accessed by the instrument vendors' proprietary software. Some commercial tools exist to convert the mass spectral data files into other formats, such as MASS Transit from PALISADE Corporation.<sup id=\"rdp-ebb-cite_ref-PALISADE_17-0\" class=\"reference\"><a href=\"#cite_note-PALISADE-17\" rel=\"external_link\">[17]<\/a><\/sup> To avoid these limitations, some efforts have been made to design and implement interoperable data formats and software libraries as for example NetCDF<sup id=\"rdp-ebb-cite_ref-NetCDF_18-0\" class=\"reference\"><a href=\"#cite_note-NetCDF-18\" rel=\"external_link\">[18]<\/a><\/sup> or mzXML.<sup id=\"rdp-ebb-cite_ref-PedrioliACommon04_19-0\" class=\"reference\"><a href=\"#cite_note-PedrioliACommon04-19\" rel=\"external_link\">[19]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-FalknerProt07_20-0\" class=\"reference\"><a href=\"#cite_note-FalknerProt07-20\" rel=\"external_link\">[20]<\/a><\/sup> But even if it is possible to convert the data files to other formats, there are drawbacks in data processing as each software implements specific functions, has its own graphical user interface and is in most cases commercially available only, as for example the applicable software of ChemStation, Xcalibur or MassLynx. Hence, the users are forced to become familiar with different software systems, user interfaces and methods. Moreover, the software tools primarily target only specific operating systems, such as Microsoft Windows and Mac OSX. The number of software applications that are independent of the operating system and can also be run under Unix or Linux is limited. Linux systems are open source, available at no cost and their usage increases in scientific research (see Scientific Linux<sup id=\"rdp-ebb-cite_ref-SciLin_21-0\" class=\"reference\"><a href=\"#cite_note-SciLin-21\" rel=\"external_link\">[21]<\/a><\/sup>), as well as in the public sector.<sup id=\"rdp-ebb-cite_ref-Wienux_22-0\" class=\"reference\"><a href=\"#cite_note-Wienux-22\" rel=\"external_link\">[22]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-LiMux_23-0\" class=\"reference\"><a href=\"#cite_note-LiMux-23\" rel=\"external_link\">[23]<\/a><\/sup> Software applications, such as AMDIS, have been published to be used free of charge, but their source code is not disposable. Thus, it is not possible to evaluate the algorithms implemented in the software. Especially in the case of scientific research, it is not possible to figure them out and to extend them. Even if algorithms are described in published papers<sup id=\"rdp-ebb-cite_ref-BillerRecon74_2-1\" class=\"reference\"><a href=\"#cite_note-BillerRecon74-2\" rel=\"external_link\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-ColbySpect92_4-1\" class=\"reference\"><a href=\"#cite_note-ColbySpect92-4\" rel=\"external_link\">[4]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-PoolBack96_9-1\" class=\"reference\"><a href=\"#cite_note-PoolBack96-9\" rel=\"external_link\">[9]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-SteinAnInt99_12-1\" class=\"reference\"><a href=\"#cite_note-SteinAnInt99-12\" rel=\"external_link\">[12]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-AlfassiOnThe04_24-0\" class=\"reference\"><a href=\"#cite_note-AlfassiOnThe04-24\" rel=\"external_link\">[24]<\/a><\/sup>, it is often impossible to validate them manually due to the complexity of chromatographic data. Other applications like ChemStation, Xcalibur, and ACD\/MS Manager are proprietary and closed source. They are only commercially available. There is no means of revealing the correctness of their utilized algorithms. Efforts have been made to solve the problems of missing interoperability and restricted access to source codes and algorithms.<sup id=\"rdp-ebb-cite_ref-SpjuthBio07_25-0\" class=\"reference\"><a href=\"#cite_note-SpjuthBio07-25\" rel=\"external_link\">[25]<\/a><\/sup> Bioclipse is a sophisticated project that is open source and is focused with its algorithms on metabolism analysis and gene sequencing. Its techniques are state-of-the-art. Some other projects are mMass<sup id=\"rdp-ebb-cite_ref-mMassArch_26-0\" class=\"reference\"><a href=\"#cite_note-mMassArch-26\" rel=\"external_link\">[26]<\/a><\/sup>, COMSPARI<sup id=\"rdp-ebb-cite_ref-COMSPARI_27-0\" class=\"reference\"><a href=\"#cite_note-COMSPARI-27\" rel=\"external_link\">[27]<\/a><\/sup> and fityk<sup id=\"rdp-ebb-cite_ref-fitykArch_28-0\" class=\"reference\"><a href=\"#cite_note-fitykArch-28\" rel=\"external_link\">[28]<\/a><\/sup>, but they do have some restrictions regarding their interoperability and extensibility. BioSunMS<sup id=\"rdp-ebb-cite_ref-CaoBio09_29-0\" class=\"reference\"><a href=\"#cite_note-CaoBio09-29\" rel=\"external_link\">[29]<\/a><\/sup> is a tool to read TOF (Time of Flight) mass spectral data files, but it is not able to read instrument vendors' native data files. The Chemistry Development Kit (CDK)<sup id=\"rdp-ebb-cite_ref-SteinbeckTheChem03_30-0\" class=\"reference\"><a href=\"#cite_note-SteinbeckTheChem03-30\" rel=\"external_link\">[30]<\/a><\/sup> implements convenient features to edit chemical data and structures, but it has no appropriate user interface. The open source tool OpenMS<sup id=\"rdp-ebb-cite_ref-SturmOpenMS08_31-0\" class=\"reference\"><a href=\"#cite_note-SturmOpenMS08-31\" rel=\"external_link\">[31]<\/a><\/sup> aims to edit mass spectrometric data, but it is not completely platform independent, as it is written in C++ programming language.\n<\/p><p>Projects like Bioclipse, Sashimi<sup id=\"rdp-ebb-cite_ref-Sashimi_32-0\" class=\"reference\"><a href=\"#cite_note-Sashimi-32\" rel=\"external_link\">[32]<\/a><\/sup> or TPP (Trans-Proteomic Pipeline)<sup id=\"rdp-ebb-cite_ref-TPP_33-0\" class=\"reference\"><a href=\"#cite_note-TPP-33\" rel=\"external_link\">[33]<\/a><\/sup> are focused on the evaluation of metabolism products and gene sequencing and make extensive use of accurate mass resolution techniques. But there is still a lack of software systems that are capable to enhance nominal mass spectral data files, that are flexible, extensible and that offer an easy to use graphical user interface. According to the authors' knowledge, no application offers functions to import vendor systems chromatographic data files and has the ability to edit and analyze chromatograms in the way ChemStation and AMDIS do. No application combines the flexibility in analyses, is easily extensible, open source, platform independent and has a configurable graphical user interface.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Implementation\">Implementation<\/span><\/h3>\n<h4><span class=\"mw-headline\" id=\"Architecture\">Architecture<\/span><\/h4>\n<p>OpenChrom is an open source software that aims to solve the aforementioned constraints getting rid of several restrictions. It is based on the Eclipse Rich Client Platform (RCP)<sup id=\"rdp-ebb-cite_ref-RCP_34-0\" class=\"reference\"><a href=\"#cite_note-RCP-34\" rel=\"external_link\">[34]<\/a><\/sup>, which is an OSGi (Open Service Gateway Initiative) based application environment that allows to build modular and flexible software systems. With the OSGi platform it is possible to extend the functionality of an application by dividing its components into different bundles. It is written in Java which is an interpreted language that depends on the Java Virtual Machine (JVM) and allows the execution of the software on several operating systems (Microsoft Windows, Mac OSX, Unix, Linux) and processor platforms (x86, PPC, AMD64, IA64, SPARC). It utilizes SWT (Standard Widget Toolkit) to render its graphical user interface by using the native resources of the underlying operating system. The Rich Client Platform is state-of-the-art in today's software development. The platform is open to be extended afterwards due to the chosen concepts. It means that the platform doesn't need to be full-fledged at the beginning. Further methods and implementations can be developed separately. Nonetheless, still some effort is necessary to design a platform that covers all needs of a software application to edit, evaluate and modify chromatographic data. In contrast to Bioclipse, Sashimi or TPP, OpenChrom has a slightly different scope, as it is focused primarily on nominal mass resolution data. Mass spectrometers for nominal mass resolution are inexpensive, as for example quadrupole or ion trap instruments. But the data acquisition limits the range of possible applications. Software has the potential to enhance the quality of the recorded data, in contrary to the given limitations. Hence, the Rich Client Platform and the Java programming language were chosen, as they offer an excellent support for a highly extensible and abstract base framework. The OSGi based Rich Client Platform Equinox supports the definition of extension points. The use of different class paths makes it possible to execute code from separated bundles (Figure 1). New functionality, e.g. to export a given chromatogram to a PDF file, can be implemented in a separate bundle making use of the extension point mechanism to import and export chromatographic data.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Wenig_BMCBioinformatics2010_11.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"de17450fa2a818c1020197da83506009\"><img alt=\"Fig1 Wenig BMCBioinformatics2010 11.jpg\" src=\"https:\/\/www.limswiki.org\/images\/5\/5d\/Fig1_Wenig_BMCBioinformatics2010_11.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 1. RCP\/OSGi and OpenChrom architecture.<\/b> The RCP\/OSGi and OpenChrom architecture shows the supported processor platforms and operating systems.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>Tools in different areas have been implemented based on the Rich Client Platform, such as the Eclipse IDE (Integrated Development Environment), Lotus Notes, Bioclipse, BioSunMS, XMind, Apache Directory Studio and several more. It is part of the OpenChrom architecture to define useful extension points and to build a suitable object model.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Object_model\">Object model<\/span><\/h4>\n<p>OpenChrom provides a designed object model to define chromatograms, scans, mass spectra, peaks and baselines. It is important to abstract the base model, as it reduces dependencies in code and allows for the implemention of further extensions. Therefore, the decision was to support an enhanced chromatogram, mass spectrum and peak model, written in Java. There is no preliminary compilation necessary on different operating systems. Further on, it is possible to cover special needs regarding the import of instrument vendors' binary chromatographic files. An excerpt of the OpenChrom object model is shown in a simplified UML (Unified Modeling Language) diagram (Figure 2). Java, as an object orientated language, supports the use of the four base strategies in object orientation: abstraction, encapsulation, polymorphic behavior and inheritance.<sup id=\"rdp-ebb-cite_ref-HorstmannCore01_35-0\" class=\"reference\"><a href=\"#cite_note-HorstmannCore01-35\" rel=\"external_link\">[35]<\/a><\/sup> OpenChrom makes extensive use of the object orientated concept. The interface \"IChromatogram\" and the abstract class \"AbstractChromatogram\" define and implement methods, which are common for all types of chromatograms, independent of the instrument vendors' data format. Therefore, it is not necessary to implement them iterative in each vendor specific chromatogram class. The base framework and extension points, like peak detectors and integrators, are working still with instances of the type \"IChromatogram\", instead of taking for example the differences of an Agilent and a NetCDF chromatogram into account. The object model for mass spectra and mass fragments, peaks and baselines is implemented in a similar way.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Wenig_BMCBioinformatics2010_11.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"cb89109044937f614ce14528aba9d786\"><img alt=\"Fig2 Wenig BMCBioinformatics2010 11.jpg\" src=\"https:\/\/www.limswiki.org\/images\/7\/7a\/Fig2_Wenig_BMCBioinformatics2010_11.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 2. OpenChrom chromatogram object model.<\/b> The OpenChrom chromatogram object model shows a simplified UML diagram of the chromatographic model OpenChrom uses.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h4><span class=\"mw-headline\" id=\"Extension_points\">Extension points<\/span><\/h4>\n<p>The OpenChrom framework offers several bundles (Table 1). The most important one defines methods to implement specialized bundles that handle the import of chromatographic mass spectral data. It is possible to supply a bundle that is able to read binary chromatogram files, given by a specific instrument vendor. The bundle takes care of how to read a given file or directory. Furthermore, the framework offers extension points to detect and integrate peaks. The peak detection and integration have been separated, to make it possible to detect peaks with several peak detector methods and to integrate them with a specified integrator. This results in a more complex but also more flexible system. There is another extension point that allows to define bundles that are capable of detecting a baseline in the chromatogram model. Another flexible extension point was introduced, called filters. Bundles can extend the filter extension point to achieve a quality enhancement of the chromatographic data. They work comparable to filters in image processing software. One filter extension can for instance offer a set of methods to eliminate background signals from the chromatogram. Another filter can implement a routine to mean normalize the chromatogram. The filters offer editing steps, which are especially useful before peak detection and integration routines.\n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" colspan=\"2\"><b>Table 1. Some selected bundles of the OpenChrom software.<\/b> The OpenChrom software offers several extension points. Extension points are declared in bundles. The table shows a selected overview of bundles and suppliers.\n<\/td><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">Bundle\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Description\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">baseline.detector\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Detect baselines\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">comparison\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Compare chromatograms and mass spectra\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">converter\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Converter to read binary\/textual data files\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">converter.supplier.agilent\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Read Agilent data files\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">converter.supplier.cdf\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Read and write NetCDF data files\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">filter\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Modify chromatographic data\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">identifier\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Identify chromatograms, mass spectra and peaks\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">integrator\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Integrate peaks\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">model\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Models (chromatogram, mass spectrum, peak,...)\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">peak.detector\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Detect peaks\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">logging\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Logging facility\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">rcp\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Base application\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">thirdpartylibraries.*\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Third party libraries (SWTChart, log4j,...)\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h4><span class=\"mw-headline\" id=\"Graphical_user_interface\">Graphical user interface<\/span><\/h4>\n<p>The Rich Client Platform offers a wide support to present an appropriate graphical user interface. Concepts detailing this include editors, views, perspectives, wizards, menus, cheat sheets, settings and help pages. OpenChrom makes extensive use of the available concepts. The editor shows the graphical representation of a chromatogram and several options, as for example a page to select or exclude distinct mass fragments. It also supports functions to save, edit and analyze chromatograms. The views are used to show different aspects of the chromatographic model. It is possible to show peaks in different kind of views. One view could show a peak including the background of the chromatogram. Another could show the peak with its increasing and decreasing tangents and its width at 50% height. A flexible mechanism was introduced to inform all views if the chromatogram selection has been changed. The update functionality is also realized by an extension point. Views and editors are composed in a task specific way using perspectives.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results_and_discussion\">Results and discussion<\/span><\/h2>\n<p>The OpenChrom software offers several options to edit and evaluate chromatographic data. It currently implements native converters to import mass spectrometric chromatograms from Agilent Technologies and to import and export NetCDF and mzXML files as well as a custom <a href=\"https:\/\/www.limswiki.org\/index.php\/XML\" title=\"XML\" class=\"mw-redirect wiki-link\" target=\"_blank\" data-key=\"fda82e3b4db7e4b2856b016933a1d2d1\">XML<\/a> format to store the chromatographic data and additional information. The chromatogram file explorer (Figure 3) shows a representation of the local file system and marks those files and directories that contain importable chromatographic data files or directories. The chromatogram can either be stored in a file, a directory or a set of files, as the converter extension point and the import and export converters take care of it. The chromatogram will be opened by a double click on the file. Additionally, a preview of the selected chromatogram file is shown in a specialized view in the user interface. The chromatogram itself is shown in a multi-page editor that is divided into a chromatogram as well as an options page. It is possible to save the chromatogram in several file formats. The NetCDF, mzXML and the customized OpenChrom XML format are actually supported. Nonetheless, the time to import and to save a chromatogram depends on its format and size. It takes more time to process XML based formats like mzXML than binary formats like NetCDF or Agilents data format. The graphical elements are drawn using SWTChart and SWT. Chromatogram selections can be chosen by applying a \"zoom in\" or \"zoom out\" action in the chromatogram editor. All views will be updated after a zoom action.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Wenig_BMCBioinformatics2010_11.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"d8f46f894ffce0f48d8ed5b923ec5669\"><img alt=\"Fig3 Wenig BMCBioinformatics2010 11.jpg\" src=\"https:\/\/www.limswiki.org\/images\/a\/a2\/Fig3_Wenig_BMCBioinformatics2010_11.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 3. OpenChrom software showing editors, views, menus and menu entries.<\/b> The OpenChrom software is using editors, views, menus and menu entries showed in the figure.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>The menu \"Chromatogram Edit\" allows to access functions that modify or evaluate the chromatographic data. For example, all registered bundles that support filters will be listed in the sub menu \"Filter\". It is possible to add a filter that implements a Savitzky-Golay<sup id=\"rdp-ebb-cite_ref-SavitzkySmooth64_36-0\" class=\"reference\"><a href=\"#cite_note-SavitzkySmooth64-36\" rel=\"external_link\">[36]<\/a><\/sup> smoothing operation or to add filters that remove the background of the chromatogram. Each action will be performed on the active chromatogram selection. Actions are commonly very fast, due to the fact that the chromatogram is kept in the random access memory (RAM), depending on the implemented algorithms. Furthermore, the filter actions are reversible. This editing support is well known from modern IDEs and office suites. But the support for do\/undo and redo operations does cost processing time. If the reversibility is not needed, it can be deactivated in the applications preference dialog. Another extension point is responsible to register baseline detectors. Different baseline detectors can be implemented in separated bundles and will be offered in the \"Baseline Detectors\" sub menu. Peak detection and integration are done commonly in one run. One improvement achieved through OpenChrom is a division of the detection and the integration of peaks into two separated actions. The peak detectors can be applied by calling an appropriate detector in the sub menu \"Peak Detectors\" and the peak integration can be performed by using an listed integrator from the sub menu \"Integrators\". The separation of detector and integrator methods makes it possible to detect peaks in a chromatogram using several algorithms and methods. The chosen peak detectors could be of different types, as for example detectors using deconvolution techniques like AMDIS or CODA. All detected peaks can afterwards be integrated by a unique integrator, which leads to comparable results. This feature offers a high flexibility in using different kinds of detectors and integrators.\n<\/p><p>The view mechanism of the Eclipse Rich Client Platform makes it possible to show chromatographic data in different kind of views. A peak can be displayed in multiple ways, for example by its area (Figure 4), its increasing and decreasing tangents and its width at 50% of peak height. Thus, the system provides additional graphical information, especially useful for educational purposes. Each view can be shown in a small (Figure 3) and extended format (Figure 4 and 5), which allows an appropriate user interaction even on small displays.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_Wenig_BMCBioinformatics2010_11.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"1f08d5f2d8028488f576c2f4542361f3\"><img alt=\"Fig4 Wenig BMCBioinformatics2010 11.jpg\" src=\"https:\/\/www.limswiki.org\/images\/3\/39\/Fig4_Wenig_BMCBioinformatics2010_11.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 4. Peak with increasing and decreasing tangents and its width at 50% height in extended format.<\/b> The view shows a maximized version of a selected peak.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig5_Wenig_BMCBioinformatics2010_11.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"c3993d3cc3de85e5a30dc0c2d772c5f8\"><img alt=\"Fig5 Wenig BMCBioinformatics2010 11.jpg\" src=\"https:\/\/www.limswiki.org\/images\/4\/43\/Fig5_Wenig_BMCBioinformatics2010_11.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 5. Graphical representation of a mass spectrum in extended format.<\/b> The view shows a maximized version of a selected mass spectrum.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>Further on, property views show miscellaneous values of the selected chromatogram. Due to the chromatogram object model, different values will be shown if different chromatogram files have been loaded. Chromatograms from Agilent Technologies and NetCDF differ in their information content. Hence, the properties view helps to inspect the files. There are additional extension points implemented that enable adding bundles to compare mass spectra using different methods<sup id=\"rdp-ebb-cite_ref-AlfassiOnThe04_24-1\" class=\"reference\"><a href=\"#cite_note-AlfassiOnThe04-24\" rel=\"external_link\">[24]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-McLaffertyComp98_37-0\" class=\"reference\"><a href=\"#cite_note-McLaffertyComp98-37\" rel=\"external_link\">[37]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-LohExact91_38-0\" class=\"reference\"><a href=\"#cite_note-LohExact91-38\" rel=\"external_link\">[38]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-DamenSiscom78_39-0\" class=\"reference\"><a href=\"#cite_note-DamenSiscom78-39\" rel=\"external_link\">[39]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-AlfassiVector05_40-0\" class=\"reference\"><a href=\"#cite_note-AlfassiVector05-40\" rel=\"external_link\">[40]<\/a><\/sup> or to identify peaks or chromatograms. A method similar to the one implemented in the software F-Search<sup id=\"rdp-ebb-cite_ref-FrontLab_41-0\" class=\"reference\"><a href=\"#cite_note-FrontLab-41\" rel=\"external_link\">[41]<\/a><\/sup> from Frontier Laboratories Ltd. could be used to identify chromatograms, for example.\n<\/p><p>Moreover, the OpenChrom platform supports bundles with a system built-in logging mechanism that extends the Apache project log4j. Each module can use the logging mechanism which makes it easier to detect problems and failures. Bundles are further separated into fragments, which allows the separation of concerns. Each OpenChrom bundle supports an internationalization (i18n) and JUnit test fragment. At the moment, approximately 3000 unit tests are written and can be executed to ensure the quality of the software.\n<\/p><p>If necessary, the extension point mechanism gives the flexibility to add functions needed by users at any time. Thus, OpenChrom can be connected to other systems, as for example to LIMS (<a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" target=\"_blank\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">Laboratory Information Management System<\/a>), databases, existing software tools or workflow systems. The object model of OpenChrom offers a convenient access to values and results from the edited chromatograms. Specialized modules take care of how to handle specific concerns, for example how to store results in an information management system. Further on, it is possible to implement bundles for specific analyses or for an automated experimentation.\n<\/p><p>OpenChrom enables several ways to edit and analyze chromatographic data. The advantage of the flexibility and the abstract architecture makes it partly difficult to get started with the platform, even if the functionality is provided by different bundles to decrease its complexity and to focus on special tasks. The intention to publish the software under an open source license is to support code contributions and to open the project for individual solutions. Moreover, the separation into bundles makes it easier for others to contribute new functionality. Further improvements will be done to optimize the current algorithms and to develop new and better filters, peak detectors and integrators.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions_2\">Conclusions<\/span><\/h2>\n<p>OpenChrom has been designed to become an extensible cross-platform open source software for the mass spectrometric analysis of chromatographic data. It provides extension points to enable built-in import capabilities for binary or textual instrument vendors' data formats. In addition to its custom XML format it supports the Agilent Technologies, mzXML and NetCDF mass spectrometric data format. Further development is planned to support more data formats. The open source concept has been chosen to initiate the contributions of third parties, as it depends on the ideas and needs of the community to extend the capabilities of the presented concept. OpenChrom offers extension points that enable the implementation of different baseline detectors as well as peak detectors and integrators. Furthermore, there is an option to implement filters, used to increase the chromatographic quality. The framework offers a full support of do\/undo and redo operations. The examples Bioclipse and BioSunMS show how to use the Eclipse Rich Client Platform in a specific way, but no software has been published until now that is capable to import binary chromatographic files natively, offers support to edit and analyze chromatograms and makes it possible to implement new algorithms and methods. As it is open source, everybody has the possibility to inspect the implemented algorithms and methods, especially for verification. OpenChrom is a software with a special focus on the editing and evaluation of mass spectrometric chromatographic data. OpenChrom will be hopefully extended by contributing developers, scientists and companies in the future.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Availability_and_requirements\">Availability and requirements<\/span><\/h2>\n<p><b>Project name<\/b>: OpenChrom\n<\/p><p><b>Project homepage<\/b>: <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.openchrom.net\" target=\"_blank\">http:\/\/\u200bwww.\u200bopenchrom.\u200bnet<\/a>\n<\/p><p><b>Operating systems<\/b>: Platform independent\n<\/p><p><b>Programming language<\/b>: Java\n<\/p><p><b>Java Runtime Environment<\/b>: Sun\/Oracle JVM 1.6.0, OpenJDK\n<\/p><p><b>Minimum RAM<\/b>: 500 MB\n<\/p><p><b>Minimum Processor<\/b>: 1 GHz\n<\/p><p><b>Commercial restrictions<\/b>: None\n<\/p><p>OpenChrom is available for download free of charge from the project home page.\n<\/p><p>The Agilent data file input converter must be installed separately using the OpenChrom update mechanism. The instructions how to install the converter can be found at the following website: <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/marketplace.openchrom.net\/\" target=\"_blank\">https:\/\/marketplace.openchrom.net\/<\/a>.\n<\/p><p>OpenChrom is licensed under the Eclipse Public License 1.0 (EPL). The EPL is an OSI approved open source license that ensures, that the source code will remain open source. OpenChrom uses some third party libraries that are partly published under different open source licenses. All third party libraries are available in separated bundles, to ensure that no license conflicts occur. The third party library bundles are published under the Apache, LGPL, AGPL and EPL license, depending on the bundle. The GPL licenses are viral, it means that derivative works must be published under the GPL license too. The EPL and Eclipse Rich Client Platform enable a different licensing for the bundles, as a bundle using methods of another bundle can not be seen as a derivative work, though it only uses its interfaces.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Declarations\">Declarations<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h3>\n<p>The authors thank all participants at the Department of Wood Science (University of Hamburg, Germany) for their support and their helpful suggestions.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Authors.E2.80.99_original_submitted_files_for_images\">Authors\u2019 original submitted files for images<\/span><\/h3>\n<p>Below are the links to the authors\u2019 original submitted files for images.\n<\/p>\n<ul><li> <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/static-content.springer.com\/esm\/art%3A10.1186%2F1471-2105-11-405\/MediaObjects\/12859_2010_3862_MOESM1_ESM.png\" target=\"_blank\">12859_2010_3862_MOESM1_ESM.png<\/a> Authors\u2019 original file for figure 1<\/li>\n<li> <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/static-content.springer.com\/esm\/art%3A10.1186%2F1471-2105-11-405\/MediaObjects\/12859_2010_3862_MOESM2_ESM.png\" target=\"_blank\">12859_2010_3862_MOESM2_ESM.png<\/a> Authors\u2019 original file for figure 2<\/li>\n<li> <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/static-content.springer.com\/esm\/art%3A10.1186%2F1471-2105-11-405\/MediaObjects\/12859_2010_3862_MOESM3_ESM.png\" target=\"_blank\">12859_2010_3862_MOESM3_ESM.png<\/a> Authors\u2019 original file for figure 3<\/li>\n<li> <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/static-content.springer.com\/esm\/art%3A10.1186%2F1471-2105-11-405\/MediaObjects\/12859_2010_3862_MOESM4_ESM.png\" target=\"_blank\">12859_2010_3862_MOESM4_ESM.png<\/a> Authors\u2019 original file for figure 4<\/li>\n<li> <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/static-content.springer.com\/esm\/art%3A10.1186%2F1471-2105-11-405\/MediaObjects\/12859_2010_3862_MOESM5_ESM.png\" target=\"_blank\">12859_2010_3862_MOESM5_ESM.png<\/a> Authors\u2019 original file for figure 5<\/li><\/ul>\n<h3><span class=\"mw-headline\" id=\"Authors.27_contributions\">Authors' contributions<\/span><\/h3>\n<p>PW designed and implemented the core API (Application Programming Interface), the software and its extension points. PW drafted most of the manuscript. JO gave feedback and corrected the manuscript. All authors performed extensive testing of the software and approved the final manuscript.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<ol class=\"references\">\n<li id=\"cite_note-BillerIdent77-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-BillerIdent77_1-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Biller, J.E.; Herlihy, W.C.; Biemann, K. 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(1997). \"Automated extraction of pure mass spectra from gas chromatographic\/mass spectrometric data\". <i>Journal Of Mass Spectrometry<\/i> <b>32<\/b> (4): 438\u2013443. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2F%28SICI%291096-9888%28199704%2932%3A4%3C438%3A%3AAID-JMS499%3E3.0.CO%3B2-N\" target=\"_blank\">10.1002\/(SICI)1096-9888(199704)32:4<438::AID-JMS499>3.0.CO;2-N<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Automated+extraction+of+pure+mass+spectra+from+gas+chromatographic%2Fmass+spectrometric+data&rft.jtitle=Journal+Of+Mass+Spectrometry&rft.aulast=Pool%2C+W.G.%3B+deLeeuw%2C+J.W.%3B+vandeGraaf%2C+B.&rft.au=Pool%2C+W.G.%3B+deLeeuw%2C+J.W.%3B+vandeGraaf%2C+B.&rft.date=1997&rft.volume=32&rft.issue=4&rft.pages=438%E2%80%93443&rft_id=info:doi\/10.1002%2F%28SICI%291096-9888%28199704%2932%3A4%3C438%3A%3AAID-JMS499%3E3.0.CO%3B2-N&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-DaviesTheNew98-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-DaviesTheNew98_11-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Davies, A. 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Wikimedia Foundation, Inc<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/en.wikipedia.org\/wiki\/Scientific_Linux\" target=\"_blank\">https:\/\/en.wikipedia.org\/wiki\/Scientific_Linux<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Scientific+Linux&rft.atitle=Wikipedia&rft.pub=Wikimedia+Foundation%2C+Inc&rft_id=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FScientific_Linux&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-Wienux-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-Wienux_22-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/en.wikipedia.org\/wiki\/Wienux\" target=\"_blank\">\"Wienux\"<\/a>. <i>Wikipedia<\/i>. Wikimedia Foundation, Inc<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/en.wikipedia.org\/wiki\/Wienux\" target=\"_blank\">https:\/\/en.wikipedia.org\/wiki\/Wienux<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Wienux&rft.atitle=Wikipedia&rft.pub=Wikimedia+Foundation%2C+Inc&rft_id=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FWienux&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LiMux-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-LiMux_23-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.muenchen.de\/rathaus\/Stadtverwaltung\/Direktorium\/LiMux.html\" target=\"_blank\">\"Das Projekt LiMux\"<\/a>. Portal M\u00fcnchen Betriebs-GmbH & Co. KG<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.muenchen.de\/rathaus\/Stadtverwaltung\/Direktorium\/LiMux.html\" target=\"_blank\">http:\/\/www.muenchen.de\/rathaus\/Stadtverwaltung\/Direktorium\/LiMux.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Das+Projekt+LiMux&rft.atitle=&rft.pub=Portal+M%C3%BCnchen+Betriebs-GmbH+%26+Co.+KG&rft_id=http%3A%2F%2Fwww.muenchen.de%2Frathaus%2FStadtverwaltung%2FDirektorium%2FLiMux.html&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-AlfassiOnThe04-24\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-AlfassiOnThe04_24-0\" rel=\"external_link\">24.0<\/a><\/sup> <sup><a href=\"#cite_ref-AlfassiOnThe04_24-1\" rel=\"external_link\">24.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Alfassi, Z.B. (2004). \"On the normalization of a mass spectrum for comparison of two spectra\". <i>Journal of the American Society for Mass Spectrometry<\/i> <b>15<\/b> (3): 385-387. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jasms.2003.11.008\" target=\"_blank\">10.1016\/j.jasms.2003.11.008<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/14998540\" target=\"_blank\">14998540<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=On+the+normalization+of+a+mass+spectrum+for+comparison+of+two+spectra&rft.jtitle=Journal+of+the+American+Society+for+Mass+Spectrometry&rft.aulast=Alfassi%2C+Z.B.&rft.au=Alfassi%2C+Z.B.&rft.date=2004&rft.volume=15&rft.issue=3&rft.pages=385-387&rft_id=info:doi\/10.1016%2Fj.jasms.2003.11.008&rft_id=info:pmid\/14998540&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SpjuthBio07-25\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SpjuthBio07_25-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Spjuth, O.; Helmus, T.; Willighagen, E.L. et al. (2007). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1808478\" target=\"_blank\">\"Bioclipse: An open source workbench for chemo- and bioinformatics\"<\/a>. <i>BMC Bioinformatics<\/i> <b>8<\/b>: 59. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2105-8-59\" target=\"_blank\">10.1186\/1471-2105-8-59<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1808478\/\" target=\"_blank\">PMC1808478<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17316423\" target=\"_blank\">17316423<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1808478\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1808478<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Bioclipse%3A+An+open+source+workbench+for+chemo-+and+bioinformatics&rft.jtitle=BMC+Bioinformatics&rft.aulast=Spjuth%2C+O.%3B+Helmus%2C+T.%3B+Willighagen%2C+E.L.+et+al.&rft.au=Spjuth%2C+O.%3B+Helmus%2C+T.%3B+Willighagen%2C+E.L.+et+al.&rft.date=2007&rft.volume=8&rft.pages=59&rft_id=info:doi\/10.1186%2F1471-2105-8-59&rft_id=info:pmc\/PMC1808478&rft_id=info:pmid\/17316423&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC1808478&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-mMassArch-26\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-mMassArch_26-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/web.archive.org\/web\/20090827071924\/http:\/\/mmass.biographics.cz\/\" target=\"_blank\">\"mMass - Open Source Mass Spectrometry Tool\"<\/a>. Martin Strohalm. Archived from <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/mmass.biographics.cz\/\" target=\"_blank\">the original<\/a> on 27 August 2009<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/web.archive.org\/web\/20090827071924\/http:\/\/mmass.biographics.cz\/\" target=\"_blank\">https:\/\/web.archive.org\/web\/20090827071924\/http:\/\/mmass.biographics.cz\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=mMass+-+Open+Source+Mass+Spectrometry+Tool&rft.atitle=&rft.pub=Martin+Strohalm&rft_id=https%3A%2F%2Fweb.archive.org%2Fweb%2F20090827071924%2Fhttp%3A%2F%2Fmmass.biographics.cz%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-COMSPARI-27\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-COMSPARI_27-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.biomechanic.org\/comspari\/\" target=\"_blank\">\"The COMSPARI Homepage\"<\/a>. J. Katz and J. Hau<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.biomechanic.org\/comspari\/\" target=\"_blank\">http:\/\/www.biomechanic.org\/comspari\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=The+COMSPARI+Homepage&rft.atitle=&rft.pub=J.+Katz+and+J.+Hau&rft_id=http%3A%2F%2Fwww.biomechanic.org%2Fcomspari%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-fitykArch-28\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-fitykArch_28-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/web.archive.org\/web\/20100304192315\/http:\/\/www.unipress.waw.pl\/fityk\" target=\"_blank\">\"Fityk home\"<\/a>. Institute of High Pressure Physics of the Polish Academy of Sciences. Archived from <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.unipress.waw.pl\/fityk\/\" target=\"_blank\">the original<\/a> on 04 March 2010<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/web.archive.org\/web\/20100304192315\/http:\/\/www.unipress.waw.pl\/fityk\" target=\"_blank\">https:\/\/web.archive.org\/web\/20100304192315\/http:\/\/www.unipress.waw.pl\/fityk<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Fityk+home&rft.atitle=&rft.pub=Institute+of+High+Pressure+Physics+of+the+Polish+Academy+of+Sciences&rft_id=https%3A%2F%2Fweb.archive.org%2Fweb%2F20100304192315%2Fhttp%3A%2F%2Fwww.unipress.waw.pl%2Ffityk&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-CaoBio09-29\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-CaoBio09_29-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Cao, Y.; Wang, N.; Ying, X.M. et al. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1808478\" target=\"_blank\">\"BioSunMS: A plug-in-based software for the management of patients information and the analysis of peptide profiles from mass spectrometry\"<\/a>. <i>BMC Medical Informatics and Decision Making<\/i> <b>9<\/b>: 13. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1472-6947-9-13\" target=\"_blank\">10.1186\/1472-6947-9-13<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1808478\/\" target=\"_blank\">PMC1808478<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17316423\" target=\"_blank\">17316423<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1808478\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1808478<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=BioSunMS%3A+A+plug-in-based+software+for+the+management+of+patients+information+and+the+analysis+of+peptide+profiles+from+mass+spectrometry&rft.jtitle=BMC+Medical+Informatics+and+Decision+Making&rft.aulast=Cao%2C+Y.%3B+Wang%2C+N.%3B+Ying%2C+X.M.+et+al.&rft.au=Cao%2C+Y.%3B+Wang%2C+N.%3B+Ying%2C+X.M.+et+al.&rft.date=2009&rft.volume=9&rft.pages=13&rft_id=info:doi\/10.1186%2F1472-6947-9-13&rft_id=info:pmc\/PMC1808478&rft_id=info:pmid\/17316423&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC1808478&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SteinbeckTheChem03-30\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SteinbeckTheChem03_30-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Steinbeck, C.; Han, Y.Q.; Kuhn, S. et al. (2003). \"The Chemistry Development Kit (CDK): An open-source Java library for Chemo- and Bioinformatics\". <i>Journal of Chemical Information and Computer Sciences<\/i> <b>43<\/b> (2): 493\u2013500. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12653513\" target=\"_blank\">12653513<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Chemistry+Development+Kit+%28CDK%29%3A+An+open-source+Java+library+for+Chemo-+and+Bioinformatics&rft.jtitle=Journal+of+Chemical+Information+and+Computer+Sciences&rft.aulast=Steinbeck%2C+C.%3B+Han%2C+Y.Q.%3B+Kuhn%2C+S.+et+al.&rft.au=Steinbeck%2C+C.%3B+Han%2C+Y.Q.%3B+Kuhn%2C+S.+et+al.&rft.date=2003&rft.volume=43&rft.issue=2&rft.pages=493%E2%80%93500&rft_id=info:pmid\/12653513&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SturmOpenMS08-31\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SturmOpenMS08_31-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sturm, M.; Bertsch, A.; Gropl, C. et al. (2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2311306\" target=\"_blank\">\"OpenMS \u2013 An open-source software framework for mass spectrometry\"<\/a>. <i>BMC Bioinformatics<\/i> <b>9<\/b>: 163. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2105-9-163\" target=\"_blank\">10.1186\/1471-2105-9-163<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2311306\/\" target=\"_blank\">PMC2311306<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18366760\" target=\"_blank\">18366760<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2311306\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2311306<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=OpenMS+%E2%80%93+An+open-source+software+framework+for+mass+spectrometry&rft.jtitle=BMC+Bioinformatics&rft.aulast=Sturm%2C+M.%3B+Bertsch%2C+A.%3B+Gropl%2C+C.+et+al.&rft.au=Sturm%2C+M.%3B+Bertsch%2C+A.%3B+Gropl%2C+C.+et+al.&rft.date=2008&rft.volume=9&rft.pages=163&rft_id=info:doi\/10.1186%2F1471-2105-9-163&rft_id=info:pmc\/PMC2311306&rft_id=info:pmid\/18366760&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2311306&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-Sashimi-32\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-Sashimi_32-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/sourceforge.net\/projects\/sashimi\/\" target=\"_blank\">\"Sashimi\"<\/a>. SourceForge<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/sourceforge.net\/projects\/sashimi\/\" target=\"_blank\">http:\/\/sourceforge.net\/projects\/sashimi\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Sashimi&rft.atitle=&rft.pub=SourceForge&rft_id=http%3A%2F%2Fsourceforge.net%2Fprojects%2Fsashimi%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-TPP-33\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-TPP_33-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/tools.proteomecenter.org\/\" target=\"_blank\">\"Seattle Proteome Center (SPC) - Proteomics Tools\"<\/a>. Institute for System Biology<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/tools.proteomecenter.org\/\" target=\"_blank\">http:\/\/tools.proteomecenter.org\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Seattle+Proteome+Center+%28SPC%29+-+Proteomics+Tools&rft.atitle=&rft.pub=Institute+for+System+Biology&rft_id=http%3A%2F%2Ftools.proteomecenter.org%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-RCP-34\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-RCP_34-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/wiki.eclipse.org\/Rich_Client_Platform\" target=\"_blank\">\"Rich Client Platform\"<\/a>. The Eclipse Foundation<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/wiki.eclipse.org\/Rich_Client_Platform\" target=\"_blank\">http:\/\/wiki.eclipse.org\/Rich_Client_Platform<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Rich+Client+Platform&rft.atitle=&rft.pub=The+Eclipse+Foundation&rft_id=http%3A%2F%2Fwiki.eclipse.org%2FRich_Client_Platform&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-HorstmannCore01-35\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-HorstmannCore01_35-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Horstmann, C.S.; Cornell, G. (2001). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/books.google.com\/books?id=W6bomXWB-TYC\" target=\"_blank\"><i>Core Java 2: Fundamentals<\/i><\/a>. Upper Saddle River, NJ: Prentice Hall Professional. pp. 806. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" target=\"_blank\">ISBN<\/a> 9780130894687<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/books.google.com\/books?id=W6bomXWB-TYC\" target=\"_blank\">https:\/\/books.google.com\/books?id=W6bomXWB-TYC<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Core+Java+2%3A+Fundamentals&rft.aulast=Horstmann%2C+C.S.%3B+Cornell%2C+G.&rft.au=Horstmann%2C+C.S.%3B+Cornell%2C+G.&rft.date=2001&rft.pages=pp.%26nbsp%3B806&rft.place=Upper+Saddle+River%2C+NJ&rft.pub=Prentice+Hall+Professional&rft.isbn=9780130894687&rft_id=https%3A%2F%2Fbooks.google.com%2Fbooks%3Fid%3DW6bomXWB-TYC&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SavitzkySmooth64-36\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SavitzkySmooth64_36-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Savitzky, A.; Golay, M.J.E. (1964). \"Smoothing and differentiation of data by simplified least squares procedures\". <i>Analytical Chemistry<\/i> <b>36<\/b> (8): 1627\u20131639. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1021%2Fac60214a047\" target=\"_blank\">10.1021\/ac60214a047<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Smoothing+and+differentiation+of+data+by+simplified+least+squares+procedures&rft.jtitle=Analytical+Chemistry&rft.aulast=Savitzky%2C+A.%3B+Golay%2C+M.J.E.&rft.au=Savitzky%2C+A.%3B+Golay%2C+M.J.E.&rft.date=1964&rft.volume=36&rft.issue=8&rft.pages=1627%E2%80%931639&rft_id=info:doi\/10.1021%2Fac60214a047&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-McLaffertyComp98-37\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-McLaffertyComp98_37-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">McLafferty, F.W.; Zhang, M.Y.; Stauffer, D.B.; Loh, S.Y. (1998). \"Comparison of algorithms and databases for matching unknown mass spectra\". <i>Journal of the American Society for Mass Spectrometry<\/i> <b>9<\/b> (1): 92-95. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS1044-0305%2897%2900235-3\" target=\"_blank\">10.1016\/S1044-0305(97)00235-3<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/9679594\" target=\"_blank\">9679594<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Comparison+of+algorithms+and+databases+for+matching+unknown+mass+spectra&rft.jtitle=Journal+of+the+American+Society+for+Mass+Spectrometry&rft.aulast=McLafferty%2C+F.W.%3B+Zhang%2C+M.Y.%3B+Stauffer%2C+D.B.%3B+Loh%2C+S.Y.&rft.au=McLafferty%2C+F.W.%3B+Zhang%2C+M.Y.%3B+Stauffer%2C+D.B.%3B+Loh%2C+S.Y.&rft.date=1998&rft.volume=9&rft.issue=1&rft.pages=92-95&rft_id=info:doi\/10.1016%2FS1044-0305%2897%2900235-3&rft_id=info:pmid\/9679594&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LohExact91-38\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-LohExact91_38-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Loh, S.Y.; McLafferty, F.W. (1991). \"Exact mass probability based matching of high-resolution unknown mass spectra\". <i>Analytical Chemistry<\/i> <b>63<\/b> (6): 546\u2013550. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1021%2Fac00006a002\" target=\"_blank\">10.1021\/ac00006a002<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Exact+mass+probability+based+matching+of+high-resolution+unknown+mass+spectra&rft.jtitle=Analytical+Chemistry&rft.aulast=Loh%2C+S.Y.%3B+McLafferty%2C+F.W.&rft.au=Loh%2C+S.Y.%3B+McLafferty%2C+F.W.&rft.date=1991&rft.volume=63&rft.issue=6&rft.pages=546%E2%80%93550&rft_id=info:doi\/10.1021%2Fac00006a002&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-DamenSiscom78-39\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-DamenSiscom78_39-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Damen, H.; Henneberg, D.; Weimann, B. (1978). \"Siscom \u2014 a new library search system for mass spectra\". <i>Analytica Chimica Acta<\/i> <b>103<\/b> (4): 289-302. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS0003-2670%2801%2983095-6\" target=\"_blank\">10.1016\/S0003-2670(01)83095-6<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Siscom+%E2%80%94+a+new+library+search+system+for+mass+spectra&rft.jtitle=Analytica+Chimica+Acta&rft.aulast=Damen%2C+H.%3B+Henneberg%2C+D.%3B+Weimann%2C+B.&rft.au=Damen%2C+H.%3B+Henneberg%2C+D.%3B+Weimann%2C+B.&rft.date=1978&rft.volume=103&rft.issue=4&rft.pages=289-302&rft_id=info:doi\/10.1016%2FS0003-2670%2801%2983095-6&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-AlfassiVector05-40\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-AlfassiVector05_40-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Alfassi, Z.B. (2005). \"Vector analysis of multi-measurements identification\". <i>Journal of Radioanalytical and Nuclear Chemistry<\/i> <b>266<\/b> (2): 245\u2013250. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs10967-005-0899-y\" target=\"_blank\">10.1007\/s10967-005-0899-y<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Vector+analysis+of+multi-measurements+identification&rft.jtitle=Journal+of+Radioanalytical+and+Nuclear+Chemistry&rft.aulast=Alfassi%2C+Z.B.&rft.au=Alfassi%2C+Z.B.&rft.date=2005&rft.volume=266&rft.issue=2&rft.pages=245%E2%80%93250&rft_id=info:doi\/10.1007%2Fs10967-005-0899-y&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-FrontLab-41\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-FrontLab_41-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.frontier-lab.com\/\" target=\"_blank\">\"Frontier Lab\"<\/a>. Frontier Laboratories Ltd<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.frontier-lab.com\/\" target=\"_blank\">http:\/\/www.frontier-lab.com\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Frontier+Lab&rft.atitle=&rft.pub=Frontier+Laboratories+Ltd&rft_id=http%3A%2F%2Fwww.frontier-lab.com%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. In the \"Conclusion\" section of the abstract, \"software\" was changed to \"chromatography software\" to encourage internal linking to the <a href=\"https:\/\/www.limswiki.org\/index.php\/CDMS\" title=\"CDMS\" class=\"mw-disambig wiki-link\" target=\"_blank\" data-key=\"97cb3168d02214cd4a6ef50bd8e55973\">CDMS<\/a> entry on the wiki. Two blank rows were removed from Table 1. A few URLS have changed since this was published in 2010, and they have been updated as needed.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192204\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.896 seconds\nReal time usage: 0.945 seconds\nPreprocessor visited node count: 29577\/1000000\nPreprocessor generated node count: 38300\/1000000\nPost\u2010expand include size: 205286\/2097152 bytes\nTemplate argument size: 66424\/2097152 bytes\nHighest expansion depth: 18\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 901.730 1 - -total\n 85.89% 774.501 1 - Template:Reflist\n 75.65% 682.138 41 - Template:Citation\/core\n 55.62% 501.539 26 - Template:Cite_journal\n 22.09% 199.209 14 - Template:Cite_web\n 8.43% 76.018 1 - Template:Infobox_journal_article\n 7.26% 65.483 1 - Template:Infobox\n 6.12% 55.170 40 - Template:Citation\/identifier\n 4.30% 38.768 80 - Template:Infobox\/row\n 3.79% 34.149 45 - Template:Citation\/make_link\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:8489-0!*!0!!en!5!* and timestamp 20181214192204 and revision id 24840\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data\">https:\/\/www.limswiki.org\/index.php\/Journal:OpenChrom:_A_cross-platform_open_source_software_for_the_mass_spectrometric_analysis_of_chromatographic_data<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","ee17c209b3c5cfdc21c7923559a9a449_images":["https:\/\/www.limswiki.org\/images\/5\/5d\/Fig1_Wenig_BMCBioinformatics2010_11.jpg","https:\/\/www.limswiki.org\/images\/7\/7a\/Fig2_Wenig_BMCBioinformatics2010_11.jpg","https:\/\/www.limswiki.org\/images\/a\/a2\/Fig3_Wenig_BMCBioinformatics2010_11.jpg","https:\/\/www.limswiki.org\/images\/3\/39\/Fig4_Wenig_BMCBioinformatics2010_11.jpg","https:\/\/www.limswiki.org\/images\/4\/43\/Fig5_Wenig_BMCBioinformatics2010_11.jpg"],"ee17c209b3c5cfdc21c7923559a9a449_timestamp":1544815323,"49a52cbdf428fd81f28d257904a1dc05_type":"article","49a52cbdf428fd81f28d257904a1dc05_title":"NG6: Integrated next generation sequencing storage and processing environment (Mariette et al. 2012)","49a52cbdf428fd81f28d257904a1dc05_url":"https:\/\/www.limswiki.org\/index.php\/Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment","49a52cbdf428fd81f28d257904a1dc05_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:NG6: Integrated next generation sequencing storage and processing environment\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nNG6: Integrated next generation sequencing storage and processing environmentJournal\n \nBMC GenomicsAuthor(s)\n \nMariette, J.; Escudi\u00e9, F.; Allias, N.; Salin, G.; Noirot, C.; Thomas, S.; Klopp, C.Author affiliation(s)\n \nBiom\u00e9trie et Intelligence Artificielle and G\u00e9n\u00e9tique CellulairePrimary contact\n \nE-mail: Jerome.Mariette@toulouse.inra.frYear published\n \n2012Volume and issue\n \n13Page(s)\n \n462DOI\n \n10.1186\/1471-2164-13-462ISSN\n \n1471-2164Distribution license\n \nCreative Commons Attribution 2.0 GenericWebsite\n \nhttp:\/\/bmcgenomics.biomedcentral.com\/articles\/10.1186\/1471-2164-13-462Download\n \nhttp:\/\/bmcgenomics.biomedcentral.com\/track\/pdf\/10.1186\/1471-2164-13-462 (PDF)\n\nContents\n\n1 Abstract \n\n1.1 Background \n1.2 Results \n1.3 Conclusions \n\n\n2 Background \n3 Implementation \n\n3.1 Building and running pipelines \n3.2 Browsing and downloading results \n3.3 Right accesses and administration \n3.4 Adding new analysis \n\n\n4 Results and discussion \n5 Conclusions \n6 Availability and requirements \n7 Declarations \n\n7.1 Acknowledgements \n7.2 Authors\u2019 original submitted files for images \n7.3 Competing interests \n7.4 Authors\u2019 contributions \n\n\n8 References \n9 Notes \n\n\n\nAbstract \nBackground \nNext generation sequencing platforms are now well implanted in sequencing centres and some laboratories. Upcoming smaller scale machines such as the 454 junior from Roche or the MiSeq from Illumina will increase the number of laboratories hosting a sequencer. In such a context, it is important to provide these teams with an easily manageable environment to store and process the produced reads.\n\nResults \nWe describe a user-friendly information system able to manage large sets of sequencing data. It includes, on one hand, a workflow environment already containing pipelines adapted to different input formats (sff, fasta, fastq and qseq), different sequencers (Roche 454, Illumina HiSeq) and various analyses (quality control, assembly, alignment, diversity studies,\u2026) and, on the other hand, a secured web site giving access to the results. The connected user will be able to download raw and processed data and browse through the analysis result statistics. The provided workflows can easily be modified or extended and new ones can be added. Ergatis is used as a workflow building, running and monitoring system. The analyses can be run locally or in a cluster environment using Sun Grid Engine.\n\nConclusions \nNG6 is a complete information system designed to answer the needs of a sequencing platform. It provides a user-friendly interface to process, store and download high-throughput sequencing data.\n\nBackground \nSequencer manufacturers follow different objectives using different platforms.[1] In the first place they release upgrades of second generation platforms producing more data with updated hardware and sequencing kits. This lowers the sequencing cost per base pair but often focuses these machines on medium or large projects. In the second place, they introduce new laboratory scale platforms such as the Illumina MiSeq or the Roche Junior which target smaller projects. And last, they work on the third generation machines which will not depend on amplified material and therefore get rid of some biases. The first two machines types which are already marketed today associated with a larger scope of sequencing protocols, enabling new studies, push towards more sequencing projects and more users.\nOnce the sequencing is done, the largest part of the work and the longest time period of the project are dedicated to data analysis. Therefore it is important to provide the new smaller production units and the laboratories in which the projects are conducted with efficient and user-friendly processing environments, enabling quality control and routine analysis. These pieces of software should have several features such as access control, metadata storage on the produced reads, quality control including known bias verification and standard analysis. NG6 was developed to match these goals and to be as flexible as possible, in order to follow sequencing technologies upgrades.\nLaboratory information management systems (LIMS) are often focused on the traceability of the biological material. Some of them, such as PIMS[2] or even SLIMS[3], have included extensions to monitor the sequencing process. However few of the open-source LIMS also provide the data processing environment. This feature is present in the Galaxy[4] sample tracking module. It is based on the Galaxy workflow engine and provides users with an interface to create and track sequencing requests. Once the sequences have been produced, the user can transfer its data files, build and run workflows to process them.\nNG6 is an extensible sequencing provider oriented LIMS. It includes read quality control and first level analysis processes which ease the data validation made jointly by the sequencing facility staff and the end-users. It provides a secured user-friendly interface to visualize and download the raw sequences files and the analysis results.\n\nImplementation \nNG6 can be split into two distinct parts: the pipelines and the web site (Figure 1). The pipelines gather a set of analyses adapted to the produced sequences. They can only be accessed and launched by the sequencing facility team. The pipelines are running in Ergatis[5]: a workflow management system able to iterate through multiple inputs in order to run them at the same time on a computer farm. These jobs perform analysis and save the analysis results in the NG6 database and directories. The web site part, presenting the results has been implemented as a TYPO3[6] extension.\n\n\n\n\n\n\n\n\n\n Figure 1. Achitecture of the ng6 application. NG6 pipelines are available within the Ergatis workflow environment. The analyses are processed either on a local system or on a distributed environment. While the analyses are running, they store the resulting files on the file system and add information about the run in the database. The produced data is then displayed by the NG6 extension of the TYPO3 CMS. Both NG6 web site and NG6 pipelines are accessible through a web browser after authentication.\n\n\n\nNG6 uses three data types: project, run and analysis. A project is a collection of runs and analysis. A run contains one or several raw files which can be used as inputs of different analysis. A project is owned by a user group and only users within this group are allowed to browse and download data related to this project.\n\nBuilding and running pipelines \nPipelines are defined by a set of connected Ergatis components. Depending on the links between the components, they are processed in a parallel or a serial manner. Most components available in NG6 combine a processing step and a storage step. This last one stores, on one hand, resulting files into the ad-hoc directory structure and, on the other hand, saves information into the database such as software version, parameters, links between analysis and resulting figures.\nIn the current version, NG6 offers a set of pipelines adapted to two platforms (Roche 454, Illumina HiSeq), four file formats (sff, fastq, fasta and qseq) and handles both Casava 1.7 and Casava 1.8 outputs of the Illumina package.[7] It includes analyses such as quality control, genomic read alignment, BAC assembly, 16S\/18S diversity analysis, expression quantification using 16S amplicons. In order to handle multiplexed runs, some pipelines first split the input read file into sample files, process and collect results on each of them and last merge these results in a summary table.\nAs an example, the 454_default pipeline processes sff files, coming from the Roche sequencer. It first performs usual statistical analysis on the reads, then tracks down contamination from common contaminant databases (ecoli, yeast and phage) using BLAST[8] returning a list of contaminated sequence IDs. Contamination between the different regions is also traced using the sfffile script included in the Roche Newbler package.[9] Sequences with incorrect MID (Multiplexed ID) are discarded and the number of contaminated sequences is returned to the end-user. Roche 454 sequencing kits include control fragments known as spike-ins within each run. Statistics on the corresponding sequences are used to check if the run matches the expected quality standard. In the next step reads are cleaned using the PyroCleaner script.[10] It discards reads considering different criteria such as length, base quality, complexity, number of undetermined bases, multiple copy reads or even faulty paired-ends. The analysis results are presented to the users in a summary table. Last, a de novo assembly is performed on the cleaned reads using the Newbler runAssembly command.[9] Some basic figures regarding the assembly results, such as contig count, N50 value, contig length distribution or even contig length versus sum of read length per contig diagram are presented to the user in order to ease the assembly quality assessment.\nWhen the pipeline execution is over, all analysis and runs newly added to the system are flagged as hidden. This was meant to permit the validation of the run by the team in charge of the sequencer before data release to the end-user.\nNG6 also provides two components enabling to start a pipeline with data already loaded into the system. The ng6run2ergatis component takes a run ID and a file pattern in order to create an input file list which can be used as input for other components. The same can be done with the ng6analysis2ergatis component to work on previous analysis result files. This enables to launch new pipelines on datasets already stored in the system in order to answer new requests. When building a new pipeline, the administrator will have the choice between several already available components such as cleaning tools : SmartKitCleaner, AdaptatorCleaner, 16Scleaner or Cutadapt[11], alignment tools : BWA[12][13], BLAST, statistical tools : FastQC[14], the SAMtools[15], 16S\/18S diversity assessment tools as mothur[16] or other utilities as fastq_extract or sff_extract.[17] After the configuration step, the administrator will be able to run the pipeline and monitor the processing steps states (Figure 2).\n\n\n\n\n\n\n\n\n\n Figure 2. Executing and monitoring workflows. To monitor, execute and create pipelines, NG6 relies on the Ergatis workflow management system. This figure presents a pipeline running on Illumina data and producing an alignment against a reference genome, some statistics on the reads, some statistics on the alignment produced and on the sought contamination.\n\n\n\nThe analyses provided in NG6 have been designed to limit the used disk space and the number of temporary files. As an example, the BWA alignment against a reference genome, performed on Illumina reads, chains BWA and SAMtools using the Unix pipe command.\nA cluster environment has often a local optimized file system. NG6 moves files from the cluster file system to the storage file system using the ng6synchronization component. Until synchronization is completed, a warning message is displayed to inform the end-user.\n\nBrowsing and downloading results \nA user can access his projects or runs using the menu bar items at the top of the page. The project and run links list all projects and runs he has access to. Once in a project, the user will see all the related runs and analysis performed on the project level. At the run level the system displays corresponding metadata such as species, sequence type and data volume. It also gives access to the sequence files and hierarchically lists analysis performed on the run. The analysis view displays analysis results and provides a direct access to the resulting data files (Figure 3). At each level, the NG6 interface shows the used disk space. The download manager accessible from the menu bar permits to select and download data and analysis results files. To avoid data duplication, if the user has an unix account on the NG6 server, the software provides the possibility to create symbolic links between the data files and his home directory.\n\n\n\n\n\n\n\n\n\n Figure 3. Administrator view of a run. The administrator view enables multiple analysis selection in order to hide, unhide or delete the selected elements. Once hidden, an analysis will no longer be displayed to the end-user. As an example, the Control analysis is displayed as hidden, so this one will not be displayed in the end-user view.\n\n\n\nAs a TYPO3 plug-in, NG6 can easily be included in any web site built with this CMS. The NG6 plug-in is compliant with the national language support system of TYPO3. Configuring the system for a new language only consists in translating and adding the corresponding language files. So far, only English and French are supported.\n\nRight accesses and administration \nNG6 offers two user status : administrator and end-user and two data access levels : public and private. Within each level the items can be hidden or unhidden. This allows to manage access rights considering the user type (Table 1). NG6 uses the TYPO3 user tables and management system. Rights are given on a project level to a user group. A user can be part of multiple groups. Once the user is logged on the web site, he can only browse projects of his groups.\n\n\n\n\n\n\n\nTable 1. Users and data right management. Considering a specified project, the administrator can browse all the runs and analysis linked to it. He is the only one with write accesses and the only one able to hide, unhide or publish a project. A connected user can browse all projects, runs and analysis that have been unhidden by the administrator. An unconnected user has only access to public projects if those ones are unhidden.\n\n\n\n\nData right level\n\n\n\n\nPublic\n\nPrivate\n\n\n\n\nHidden\n\nUnhidden\n\nHidden\n\nUnhidden\n\n\nProject administrator\n\nY\n\nY\n\nY\n\nY\n\n\nConnected user\n\nN\n\nY\n\nN\n\nY\n\n\nUnconnected user\n\nN\n\nY\n\nN\n\nN\n\n\n\nThe project administrator has all rights on the project, he can delete, hide, unhide, publish and unpublish the whole project with related runs and analysis. A hidden project is only visible to the project administrator, this was designed in order to permit the validation of the run by the team in charge of the sequencer before releasing the data to the end-user. To give access to the project, once the data is validated, the administrator unhides it. This is also true for analysis (Figure 4). The metadata fields are editable on line by the administrator.\n\n\n\n\n\n\n\n\n\n Figure 4. Example of some analysis view. The analysis result layout is defined in a smarty template, thus enabling different layouts for the end-user. Figure five shows examples of MothurClassify and PyroCleaner analysis result displays.\n\n\n\nA published project is openly accessible on the web site. For example, you can access our demonstration project using the following link : http:\/\/ng6.toulouse.inra.fr\/\u200bindex.\u200bphp?\u200bid=\u200b3. This feature provides the biologists with a fast and easy way to make their data accessible to their community.\n\nAdding new analysis \nNG6 web site is a TYPO3 extension written in PHP. It uses the Smarty template engine[18] and the jQuery JavaScript library.[19] Adding new analysis into NG6 requires three steps. The first one is writing the Ergatis component of the analysis. Each parameter, input and output required by the analysis has to be specified in the configuration file. Second, a simple Python script has to be programmed using the NG6 API and the provided skeleton to define the data stored in the database and the result files stored in the directory structure. Finally, a Smarty template is specified to set the corresponding analysis display. While writing the Smarty template, the developer has access to several objects to build the analysis display as wished. Several HTML classes are available to ease JavaScript functionalities implementation.\n\nResults and discussion \nNG6 has been in production since September 2009 at the genomic platform of GenoToul[20] and stores more than 950 runs corresponding to 96 projects and using 5\u2009TB on the hard drive. The system stores Illumina and Roche 454 runs produced by different sequencer versions. Pipelines are configured and launched by the genomic platform staff for one year.\nAssessing the quality of the produced reads is an important task for a sequencing center. Making it automatic saves a lot of time. Displaying the analysis results within a user-friendly interface eases the discussions with the end-users.\nOther read analysis environments are available to biologists. The most popular today is Galaxy. We have chosen to implement our own system because Galaxy and NG6 target different aims and focus on different users. Galaxy aims at simplifying data processing for researchers. It includes modules processing sequencing data. NG6 is a sequencing provider focused LIMS gathering specialized pipelines and website.\n\nConclusions \nNG6 is an information system providing a set of automated analysis pipelines built to process NGS (Next Generation Sequencing) data which can be executed locally or in a cluster environment. It is built upon well documented and extensively used components such as Ergatis and TYPO3. The current version of NG6 offers several pipelines but some others are under-construction: RNAseq using TopHat[21] and Cufflinks[22] and miRNA expression analysis.\n\nAvailability and requirements \nThe NG6 code is freely available on the web. To ease the installation, the package and all its dependencies are also available as a virtual machine. Installing and maintaining the system would require expertise in Linux system administration. The project is hosted in a forge environment in order to open it to the developers community.\nProject name: NG6\nProject home page: https:\/\/mulcyber.toulouse.inra.fr\/projects\/ng6\/\nOperating system(s): Platform independent\nProgramming language: Python\/PHP\nOther requirements: VMWare or VirualBox\nLicense: GNU GPL\nAny restrictions to use by non-academics: none\n\nDeclarations \nAcknowledgements \nWe would like to acknowledge the GenoToul genomic platform and the CBiB platform of Bordeaux for providing us useful feedback on the system and for pointing out us features worth developing. We thank the reviewers for their insightful and constructive comments.\n\nAuthors\u2019 original submitted files for images \nBelow are the links to the authors\u2019 original submitted files for images.\n\n 12864_2012_4188_MOESM1_ESM.tiff Authors\u2019 original file for figure 1\n 12864_2012_4188_MOESM2_ESM.tiff Authors\u2019 original file for figure 2\n 12864_2012_4188_MOESM3_ESM.tiff Authors\u2019 original file for figure 3\n 12864_2012_4188_MOESM4_ESM.tiff Authors\u2019 original file for figure 4\nCompeting interests \nThe authors declare that they have no competing interest.\n\nAuthors\u2019 contributions \nJM and CK conceived and designed the project. JM, FE, GS, CN, NA implemented NG6 pipelines and web site. JM and ST packaged NG6 into a virtual machine. JM and CK drafted the manuscript. All authors read and approved the final manuscript.\n\nReferences \n\n\n\u2191 Glenn, T.C. (2011). \"Field guide to next-generation DNA sequencers\". Molecular Ecology Resources 11 (5): 759-769. doi:10.1111\/j.1755-0998.2011.03024.x. PMID 21592312.   \n\n\u2191 Troshin, P.V. Postis, V.L.; Ashworth, D. et al. (2011). \"PIMS sequencing extension: a laboratory information management system for DNA sequencing facilities\". BMC Research Notes 4: 48. doi:10.1186\/1756-0500-4-48. PMC PMC3058032. PMID 21385349. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3058032 .   \n\n\u2191 Van Rossum, T.; Tripp, B.; Daley, D. (2010). \"SLIMS: A user-friendly sample operations and inventory management system for genotyping labs\". Bioinformatics 26 (14): 1808-1810. doi:10.1093\/bioinformatics\/btq271. PMC PMC2894515. PMID 20513665. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2894515 .   \n\n\u2191 Giardine, B.; Riemer, C.; Hardison, R.C. et al. (2005). \"Galaxy: A platform for interactive large-scale genome analysis\". Genome Research 15 (10): 1451\u20131455. doi:10.1101\/gr.4086505. PMC PMC1240089. PMID 16169926. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1240089 .   \n\n\u2191 Orvis, J.; Crabtree, J.; Galens, K. et al. (2010). \"Ergatis: A web interface and scalable software system for bioinformatics workflows\". Bioinformatics 26 (12): 1488-1492. doi:10.1093\/bioinformatics\/btq167. PMC PMC2881353. PMID 20413634. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2881353 .   \n\n\u2191 \"TYPO3\". TYPO3 Association. https:\/\/typo3.org\/ .   \n\n\u2191 \"Illumina\". Illumina, Inc. http:\/\/www.illumina.com\/ .   \n\n\u2191 Altschul, S.; Gish, W.; Miller, W.; Myers, E.; Lipman, D. (1990). \"Basic local alignment search tool\". Journal of Molecular Biology 215 (3): 403\u2013410. doi:10.1016\/S0022-2836(05)80360-2. PMID 2231712.   \n\n\u2191 9.0 9.1 \"454 Sequencing\". Roche Diagnostics Corporation. http:\/\/www.my454.com\/ .   \n\n\u2191 Mariette, J.; Noirot, C.; Klopp, C. (2011). \"Assessment of replicate bias in 454 pyrosequencing and a multi-purpose read-filtering tool\". BMC Research Notes 4: 149. doi:10.1186\/1756-0500-4-149. PMC PMC3117718. PMID 21615897. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3117718 .   \n\n\u2191 \"Cutadapt\". Marcel Martin. https:\/\/cutadapt.readthedocs.org\/en\/stable\/ .   \n\n\u2191 Li, H.; Durbin, R. (2009). \"Fast and accurate short read alignment with Burrows\u2013Wheeler transform\". Bioinformatics 25 (14): 1754\u201360. doi:10.1093\/bioinformatics\/btp324. PMC PMC2705234. PMID 19451168. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2705234 .   \n\n\u2191 Li, H.; Durbin, R. (2010). \"Fast and accurate long-read alignment with Burrows\u2013Wheeler transform\". Bioinformatics 26 (5): 589-95. doi:10.1093\/bioinformatics\/btp698. PMC PMC2828108. PMID 20080505. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2828108 .   \n\n\u2191 \"FastQC\". Babraham Bioinformatics. http:\/\/www.bioinformatics.bbsrc.ac.uk\/projects\/fastqc\/ .   \n\n\u2191 Li, H.; Handsaker, B.; Wysoker, A. et al. (2009). \"The Sequence Alignment\/Map format and SAMtools\". Bioinformatics 25 (16): 2078-9. doi:10.1093\/bioinformatics\/btp352. PMC PMC2723002. PMID 19505943. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2723002 .   \n\n\u2191 Schloss, P.D.; Westcott, S.L.; Ryabin, T. et al. (2009). \"Open-source, platform-independent, community-supported software for describing and comparing microbial communities\". Applied and Environmental Microbiology 75 (23): 7537\u20137541. doi:10.1128\/AEM.01541-09. PMC PMC2786419. PMID 19801464. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2786419 .   \n\n\u2191 \"sff_extract\". Institute for Conservation & Improvement of Valencian Agrodiversity. https:\/\/bioinf.comav.upv.es\/sff_extract\/ .   \n\n\u2191 \"Smarty Template Engine\". New Digital Group, Inc. http:\/\/www.smarty.net\/ .   \n\n\u2191 \"jQuery - Write less, do more\". The jQuery Foundation. http:\/\/jquery.com\/ .   \n\n\u2191 \"G\u00e9nome et Transcriptome\". G\u00e9nome et Transcriptome. http:\/\/get.genotoul.fr\/ .   \n\n\u2191 Trapnell, C.; Pachter, L.; Salzberg, S.L. (2009). \"TopHat: Discovering splice junctions with RNA-Seq\". Bioinformatics 25 (9): 1105\u20131111. doi:10.1093\/bioinformatics\/btp120. PMC PMC2672628. PMID 19289445. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2672628 .   \n\n\u2191 Roberts, A.; Pimentel, H.; Trapnell, C.; Pachter, L. (2011). \"dentification of novel transcripts in annotated genomes using RNA-Seq\". Bioinformatics 27 (17): 2325\u20132329. doi:10.1093\/bioinformatics\/btr355. PMID 21697122.   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. In several cases, the old URL was dead, and a new functioning URL replaced it. Additionally, numerous proper nouns were not capitalized originally but have been updated in this text. Finally, Ys and Ns have been substituted in the tables for checkmarks and Xs, respectively.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\">https:\/\/www.limswiki.org\/index.php\/Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on bioinformatics\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 15 March 2016, at 17:04.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 1,275 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","49a52cbdf428fd81f28d257904a1dc05_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_NG6_Integrated_next_generation_sequencing_storage_and_processing_environment skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:NG6: Integrated next generation sequencing storage and processing environment<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Background\">Background<\/span><\/h3>\n<p>Next generation <a href=\"https:\/\/www.limswiki.org\/index.php\/Sequencing\" title=\"Sequencing\" class=\"mw-disambig wiki-link\" target=\"_blank\" data-key=\"e36167a9eb152ca16a0c4c4e6d13f323\">sequencing<\/a> platforms are now well implanted in sequencing centres and some <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" target=\"_blank\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratories<\/a>. Upcoming smaller scale machines such as the 454 junior from Roche or the MiSeq from Illumina will increase the number of laboratories hosting a sequencer. In such a context, it is important to provide these teams with an easily manageable environment to store and process the produced reads.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h3>\n<p>We describe a user-friendly information system able to manage large sets of sequencing data. It includes, on one hand, a workflow environment already containing pipelines adapted to different input formats (sff, fasta, fastq and qseq), different sequencers (Roche 454, Illumina HiSeq) and various analyses (quality control, assembly, alignment, diversity studies,\u2026) and, on the other hand, a secured web site giving access to the results. The connected user will be able to download raw and processed data and browse through the analysis result statistics. The provided workflows can easily be modified or extended and new ones can be added. Ergatis is used as a workflow building, running and monitoring system. The analyses can be run locally or in a cluster environment using Sun Grid Engine.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h3>\n<p>NG6 is a complete information system designed to answer the needs of a sequencing platform. It provides a user-friendly interface to process, store and download high-throughput sequencing data.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Background_2\">Background<\/span><\/h2>\n<p>Sequencer manufacturers follow different objectives using different platforms.<sup id=\"rdp-ebb-cite_ref-GlennField11_1-0\" class=\"reference\"><a href=\"#cite_note-GlennField11-1\" rel=\"external_link\">[1]<\/a><\/sup> In the first place they release upgrades of second generation platforms producing more data with updated hardware and sequencing kits. This lowers the sequencing cost per base pair but often focuses these machines on medium or large projects. In the second place, they introduce new laboratory scale platforms such as the Illumina MiSeq or the Roche Junior which target smaller projects. And last, they work on the third generation machines which will not depend on amplified material and therefore get rid of some biases. The first two machines types which are already marketed today associated with a larger scope of sequencing protocols, enabling new studies, push towards more sequencing projects and more users.\n<\/p><p>Once the sequencing is done, the largest part of the work and the longest time period of the project are dedicated to data analysis. Therefore it is important to provide the new smaller production units and the laboratories in which the projects are conducted with efficient and user-friendly processing environments, enabling quality control and routine analysis. These pieces of software should have several features such as access control, metadata storage on the produced reads, quality control including known bias verification and standard analysis. NG6 was developed to match these goals and to be as flexible as possible, in order to follow sequencing technologies upgrades.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" target=\"_blank\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">Laboratory information management systems<\/a> (LIMS) are often focused on the traceability of the biological material. Some of them, such as <a href=\"https:\/\/www.limswiki.org\/index.php\/PiMS\" title=\"PiMS\" target=\"_blank\" class=\"wiki-link\" data-key=\"aa61d8159c6d0a8f4cdeca09d397701f\">PIMS<\/a><sup id=\"rdp-ebb-cite_ref-TroshinPIMS11_2-0\" class=\"reference\"><a href=\"#cite_note-TroshinPIMS11-2\" rel=\"external_link\">[2]<\/a><\/sup> or even <a href=\"https:\/\/www.limswiki.org\/index.php\/Genohm_SA#SLims\" title=\"Genohm SA\" target=\"_blank\" class=\"wiki-link\" data-key=\"4dd217548405c9fc3c964037309f20e3\">SLIMS<\/a><sup id=\"rdp-ebb-cite_ref-VanRossumSLIMS10_3-0\" class=\"reference\"><a href=\"#cite_note-VanRossumSLIMS10-3\" rel=\"external_link\">[3]<\/a><\/sup>, have included extensions to monitor the sequencing process. However few of the <a href=\"https:\/\/www.limswiki.org\/index.php\/Category:Laboratory_information_management_systems_(open_source)\" title=\"Category:Laboratory information management systems (open source)\" target=\"_blank\" class=\"wiki-link\" data-key=\"3ddf885cb75e1140d0fc0cc2480d3895\">open-source LIMS<\/a> also provide the data processing environment. This feature is present in the <a href=\"https:\/\/www.limswiki.org\/index.php\/Galaxy_(biomedical_software)\" title=\"Galaxy (biomedical software)\" target=\"_blank\" class=\"wiki-link\" data-key=\"ead5d6ebaa8d67744d2f68d454d89ce6\">Galaxy<\/a><sup id=\"rdp-ebb-cite_ref-GiarineGal05_4-0\" class=\"reference\"><a href=\"#cite_note-GiarineGal05-4\" rel=\"external_link\">[4]<\/a><\/sup> sample tracking module. It is based on the Galaxy workflow engine and provides users with an interface to create and track sequencing requests. Once the sequences have been produced, the user can transfer its data files, build and run workflows to process them.\n<\/p><p>NG6 is an extensible sequencing provider oriented LIMS. It includes read quality control and first level analysis processes which ease the data validation made jointly by the sequencing facility staff and the end-users. It provides a secured user-friendly interface to visualize and download the raw sequences files and the analysis results.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Implementation\">Implementation<\/span><\/h2>\n<p>NG6 can be split into two distinct parts: the pipelines and the web site (Figure 1). The pipelines gather a set of analyses adapted to the produced sequences. They can only be accessed and launched by the sequencing facility team. The pipelines are running in Ergatis<sup id=\"rdp-ebb-cite_ref-OrvisErgatis10_5-0\" class=\"reference\"><a href=\"#cite_note-OrvisErgatis10-5\" rel=\"external_link\">[5]<\/a><\/sup>: a workflow management system able to iterate through multiple inputs in order to run them at the same time on a computer farm. These jobs perform analysis and save the analysis results in the NG6 database and directories. The web site part, presenting the results has been implemented as a <a href=\"https:\/\/www.limswiki.org\/index.php\/TYPO3\" title=\"TYPO3\" target=\"_blank\" class=\"wiki-link\" data-key=\"a728501a1d1f1197ee6f1a5a538e1d2e\">TYPO3<\/a><sup id=\"rdp-ebb-cite_ref-TYPO3Home_6-0\" class=\"reference\"><a href=\"#cite_note-TYPO3Home-6\" rel=\"external_link\">[6]<\/a><\/sup> extension.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Mariette_BMCGenomics2015_13.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"19ad61ae85818fd3b1753c1bd3aee595\"><img alt=\"Fig1 Mariette BMCGenomics2015 13.jpg\" src=\"https:\/\/www.limswiki.org\/images\/2\/2f\/Fig1_Mariette_BMCGenomics2015_13.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 1. Achitecture of the ng6 application.<\/b> NG6 pipelines are available within the Ergatis workflow environment. The analyses are processed either on a local system or on a distributed environment. While the analyses are running, they store the resulting files on the file system and add information about the run in the database. The produced data is then displayed by the NG6 extension of the TYPO3 CMS. Both NG6 web site and NG6 pipelines are accessible through a web browser after authentication.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>NG6 uses three data types: project, run and analysis. A project is a collection of runs and analysis. A run contains one or several raw files which can be used as inputs of different analysis. A project is owned by a user group and only users within this group are allowed to browse and download data related to this project.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Building_and_running_pipelines\">Building and running pipelines<\/span><\/h3>\n<p>Pipelines are defined by a set of connected Ergatis components. Depending on the links between the components, they are processed in a parallel or a serial manner. Most components available in NG6 combine a processing step and a storage step. This last one stores, on one hand, resulting files into the ad-hoc directory structure and, on the other hand, saves information into the database such as software version, parameters, links between analysis and resulting figures.\n<\/p><p>In the current version, NG6 offers a set of pipelines adapted to two platforms (Roche 454, Illumina HiSeq), four file formats (sff, fastq, fasta and qseq) and handles both Casava 1.7 and Casava 1.8 outputs of the Illumina package.<sup id=\"rdp-ebb-cite_ref-IlluminaHome_7-0\" class=\"reference\"><a href=\"#cite_note-IlluminaHome-7\" rel=\"external_link\">[7]<\/a><\/sup> It includes analyses such as quality control, genomic read alignment, BAC assembly, 16S\/18S diversity analysis, expression quantification using 16S amplicons. In order to handle multiplexed runs, some pipelines first split the input read file into sample files, process and collect results on each of them and last merge these results in a summary table.\n<\/p><p>As an example, the 454_default pipeline processes sff files, coming from the Roche sequencer. It first performs usual statistical analysis on the reads, then tracks down contamination from common contaminant databases (ecoli, yeast and phage) using BLAST<sup id=\"rdp-ebb-cite_ref-AltschulBLAST90_8-0\" class=\"reference\"><a href=\"#cite_note-AltschulBLAST90-8\" rel=\"external_link\">[8]<\/a><\/sup> returning a list of contaminated sequence IDs. Contamination between the different regions is also traced using the sfffile script included in the Roche Newbler package.<sup id=\"rdp-ebb-cite_ref-Roche454Home_9-0\" class=\"reference\"><a href=\"#cite_note-Roche454Home-9\" rel=\"external_link\">[9]<\/a><\/sup> Sequences with incorrect MID (Multiplexed ID) are discarded and the number of contaminated sequences is returned to the end-user. Roche 454 sequencing kits include control fragments known as spike-ins within each run. Statistics on the corresponding sequences are used to check if the run matches the expected quality standard. In the next step reads are cleaned using the PyroCleaner script.<sup id=\"rdp-ebb-cite_ref-MarieteAssess11_10-0\" class=\"reference\"><a href=\"#cite_note-MarieteAssess11-10\" rel=\"external_link\">[10]<\/a><\/sup> It discards reads considering different criteria such as length, base quality, complexity, number of undetermined bases, multiple copy reads or even faulty paired-ends. The analysis results are presented to the users in a summary table. Last, a <i>de novo<\/i> assembly is performed on the cleaned reads using the Newbler runAssembly command.<sup id=\"rdp-ebb-cite_ref-Roche454Home_9-1\" class=\"reference\"><a href=\"#cite_note-Roche454Home-9\" rel=\"external_link\">[9]<\/a><\/sup> Some basic figures regarding the assembly results, such as contig count, N50 value, contig length distribution or even contig length versus sum of read length per contig diagram are presented to the user in order to ease the assembly quality assessment.\n<\/p><p>When the pipeline execution is over, all analysis and runs newly added to the system are flagged as hidden. This was meant to permit the validation of the run by the team in charge of the sequencer before data release to the end-user.\n<\/p><p>NG6 also provides two components enabling to start a pipeline with data already loaded into the system. The ng6run2ergatis component takes a run ID and a file pattern in order to create an input file list which can be used as input for other components. The same can be done with the ng6analysis2ergatis component to work on previous analysis result files. This enables to launch new pipelines on datasets already stored in the system in order to answer new requests. When building a new pipeline, the administrator will have the choice between several already available components such as cleaning tools : SmartKitCleaner, AdaptatorCleaner, 16Scleaner or Cutadapt<sup id=\"rdp-ebb-cite_ref-CutadaptHome_11-0\" class=\"reference\"><a href=\"#cite_note-CutadaptHome-11\" rel=\"external_link\">[11]<\/a><\/sup>, alignment tools : BWA<sup id=\"rdp-ebb-cite_ref-LiFastShort09_12-0\" class=\"reference\"><a href=\"#cite_note-LiFastShort09-12\" rel=\"external_link\">[12]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-LiFastLong10_13-0\" class=\"reference\"><a href=\"#cite_note-LiFastLong10-13\" rel=\"external_link\">[13]<\/a><\/sup>, BLAST, statistical tools : FastQC<sup id=\"rdp-ebb-cite_ref-FastQCHome_14-0\" class=\"reference\"><a href=\"#cite_note-FastQCHome-14\" rel=\"external_link\">[14]<\/a><\/sup>, the SAMtools<sup id=\"rdp-ebb-cite_ref-LiTheSeq09_15-0\" class=\"reference\"><a href=\"#cite_note-LiTheSeq09-15\" rel=\"external_link\">[15]<\/a><\/sup>, 16S\/18S diversity assessment tools as mothur<sup id=\"rdp-ebb-cite_ref-SchlossOpen09_16-0\" class=\"reference\"><a href=\"#cite_note-SchlossOpen09-16\" rel=\"external_link\">[16]<\/a><\/sup> or other utilities as fastq_extract or sff_extract.<sup id=\"rdp-ebb-cite_ref-sffHome_17-0\" class=\"reference\"><a href=\"#cite_note-sffHome-17\" rel=\"external_link\">[17]<\/a><\/sup> After the configuration step, the administrator will be able to run the pipeline and monitor the processing steps states (Figure 2).\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Mariette_BMCGenomics2015_13.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"15ff8ba958747e6d0746eee7b3051434\"><img alt=\"Fig2 Mariette BMCGenomics2015 13.jpg\" src=\"https:\/\/www.limswiki.org\/images\/1\/1d\/Fig2_Mariette_BMCGenomics2015_13.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 2. Executing and monitoring workflows.<\/b> To monitor, execute and create pipelines, NG6 relies on the Ergatis workflow management system. This figure presents a pipeline running on Illumina data and producing an alignment against a reference genome, some statistics on the reads, some statistics on the alignment produced and on the sought contamination.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>The analyses provided in NG6 have been designed to limit the used disk space and the number of temporary files. As an example, the BWA alignment against a reference genome, performed on Illumina reads, chains BWA and SAMtools using the Unix pipe command.\n<\/p><p>A cluster environment has often a local optimized file system. NG6 moves files from the cluster file system to the storage file system using the ng6synchronization component. Until synchronization is completed, a warning message is displayed to inform the end-user.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Browsing_and_downloading_results\">Browsing and downloading results<\/span><\/h3>\n<p>A user can access his projects or runs using the menu bar items at the top of the page. The project and run links list all projects and runs he has access to. Once in a project, the user will see all the related runs and analysis performed on the project level. At the run level the system displays corresponding metadata such as species, sequence type and data volume. It also gives access to the sequence files and hierarchically lists analysis performed on the run. The analysis view displays analysis results and provides a direct access to the resulting data files (Figure 3). At each level, the NG6 interface shows the used disk space. The download manager accessible from the menu bar permits to select and download data and analysis results files. To avoid data duplication, if the user has an unix account on the NG6 server, the software provides the possibility to create symbolic links between the data files and his home directory.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Mariette_BMCGenomics2015_13.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"79531acce7ba14cd3a8c6c98daf81244\"><img alt=\"Fig3 Mariette BMCGenomics2015 13.jpg\" src=\"https:\/\/www.limswiki.org\/images\/0\/0a\/Fig3_Mariette_BMCGenomics2015_13.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 3. Administrator view of a run.<\/b> The administrator view enables multiple analysis selection in order to hide, unhide or delete the selected elements. Once hidden, an analysis will no longer be displayed to the end-user. As an example, the Control analysis is displayed as hidden, so this one will not be displayed in the end-user view.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>As a TYPO3 plug-in, NG6 can easily be included in any web site built with this CMS. The NG6 plug-in is compliant with the national language support system of TYPO3. Configuring the system for a new language only consists in translating and adding the corresponding language files. So far, only English and French are supported.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Right_accesses_and_administration\">Right accesses and administration<\/span><\/h3>\n<p>NG6 offers two user status : administrator and end-user and two data access levels : public and private. Within each level the items can be hidden or unhidden. This allows to manage access rights considering the user type (Table 1). NG6 uses the TYPO3 user tables and management system. Rights are given on a project level to a user group. A user can be part of multiple groups. Once the user is logged on the web site, he can only browse projects of his groups.\n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" colspan=\"5\"><b>Table 1. Users and data right management.<\/b> Considering a specified project, the administrator can browse all the runs and analysis linked to it. He is the only one with write accesses and the only one able to hide, unhide or publish a project. A connected user can browse all projects, runs and analysis that have been unhidden by the administrator. An unconnected user has only access to public projects if those ones are unhidden.\n<\/td><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\" colspan=\"4\">Data right level\n<\/th><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\" colspan=\"2\">Public\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\" colspan=\"2\">Private\n<\/th><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Hidden\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Unhidden\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Hidden\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Unhidden\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Project administrator\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Connected user\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Unconnected user\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Y\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>The project administrator has all rights on the project, he can delete, hide, unhide, publish and unpublish the whole project with related runs and analysis. A hidden project is only visible to the project administrator, this was designed in order to permit the validation of the run by the team in charge of the sequencer before releasing the data to the end-user. To give access to the project, once the data is validated, the administrator unhides it. This is also true for analysis (Figure 4). The metadata fields are editable on line by the administrator.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_Mariette_BMCGenomics2015_13.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"36f742dbb99ad31db81d3fc0ac5f757d\"><img alt=\"Fig4 Mariette BMCGenomics2015 13.jpg\" src=\"https:\/\/www.limswiki.org\/images\/e\/eb\/Fig4_Mariette_BMCGenomics2015_13.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 4. Example of some analysis view.<\/b> The analysis result layout is defined in a smarty template, thus enabling different layouts for the end-user. Figure five shows examples of MothurClassify and PyroCleaner analysis result displays.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>A published project is openly accessible on the web site. For example, you can access our demonstration project using the following link : <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ng6.toulouse.inra.fr\/\u200bindex.\u200bphp?\u200bid=\u200b3\" target=\"_blank\">http:\/\/ng6.toulouse.inra.fr\/\u200bindex.\u200bphp?\u200bid=\u200b3<\/a>. This feature provides the biologists with a fast and easy way to make their data accessible to their community.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Adding_new_analysis\">Adding new analysis<\/span><\/h3>\n<p>NG6 web site is a TYPO3 extension written in PHP. It uses the Smarty template engine<sup id=\"rdp-ebb-cite_ref-SmartyHome_18-0\" class=\"reference\"><a href=\"#cite_note-SmartyHome-18\" rel=\"external_link\">[18]<\/a><\/sup> and the jQuery JavaScript library.<sup id=\"rdp-ebb-cite_ref-jQueryHome_19-0\" class=\"reference\"><a href=\"#cite_note-jQueryHome-19\" rel=\"external_link\">[19]<\/a><\/sup> Adding new analysis into NG6 requires three steps. The first one is writing the Ergatis component of the analysis. Each parameter, input and output required by the analysis has to be specified in the configuration file. Second, a simple Python script has to be programmed using the NG6 API and the provided skeleton to define the data stored in the database and the result files stored in the directory structure. Finally, a Smarty template is specified to set the corresponding analysis display. While writing the Smarty template, the developer has access to several objects to build the analysis display as wished. Several HTML classes are available to ease JavaScript functionalities implementation.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results_and_discussion\">Results and discussion<\/span><\/h2>\n<p>NG6 has been in production since September 2009 at the genomic platform of GenoToul<sup id=\"rdp-ebb-cite_ref-GenoToulHome_20-0\" class=\"reference\"><a href=\"#cite_note-GenoToulHome-20\" rel=\"external_link\">[20]<\/a><\/sup> and stores more than 950 runs corresponding to 96 projects and using 5\u2009TB on the hard drive. The system stores Illumina and Roche 454 runs produced by different sequencer versions. Pipelines are configured and launched by the genomic platform staff for one year.\n<\/p><p>Assessing the quality of the produced reads is an important task for a sequencing center. Making it automatic saves a lot of time. Displaying the analysis results within a user-friendly interface eases the discussions with the end-users.\n<\/p><p>Other read analysis environments are available to biologists. The most popular today is Galaxy. We have chosen to implement our own system because Galaxy and NG6 target different aims and focus on different users. Galaxy aims at simplifying data processing for researchers. It includes modules processing sequencing data. NG6 is a sequencing provider focused LIMS gathering specialized pipelines and website.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions_2\">Conclusions<\/span><\/h2>\n<p>NG6 is an information system providing a set of automated analysis pipelines built to process NGS (Next Generation Sequencing) data which can be executed locally or in a cluster environment. It is built upon well documented and extensively used components such as Ergatis and TYPO3. The current version of NG6 offers several pipelines but some others are under-construction: RNAseq using TopHat<sup id=\"rdp-ebb-cite_ref-TrapnellTop09_21-0\" class=\"reference\"><a href=\"#cite_note-TrapnellTop09-21\" rel=\"external_link\">[21]<\/a><\/sup> and Cufflinks<sup id=\"rdp-ebb-cite_ref-RobertsIdent11_22-0\" class=\"reference\"><a href=\"#cite_note-RobertsIdent11-22\" rel=\"external_link\">[22]<\/a><\/sup> and miRNA expression analysis.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Availability_and_requirements\">Availability and requirements<\/span><\/h2>\n<p>The NG6 code is freely available on the web. To ease the installation, the package and all its dependencies are also available as a virtual machine. Installing and maintaining the system would require expertise in Linux system administration. The project is hosted in a forge environment in order to open it to the developers community.\n<\/p><p>Project name: NG6\n<\/p><p>Project home page: <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/mulcyber.toulouse.inra.fr\/projects\/ng6\/\" target=\"_blank\">https:\/\/mulcyber.toulouse.inra.fr\/projects\/ng6\/<\/a>\n<\/p><p>Operating system(s): Platform independent\n<\/p><p>Programming language: Python\/PHP\n<\/p><p>Other requirements: VMWare or VirualBox\n<\/p><p>License: GNU GPL\n<\/p><p>Any restrictions to use by non-academics: none\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Declarations\">Declarations<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h3>\n<p>We would like to acknowledge the GenoToul genomic platform and the CBiB platform of Bordeaux for providing us useful feedback on the system and for pointing out us features worth developing. We thank the reviewers for their insightful and constructive comments.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Authors.E2.80.99_original_submitted_files_for_images\">Authors\u2019 original submitted files for images<\/span><\/h3>\n<p>Below are the links to the authors\u2019 original submitted files for images.\n<\/p>\n<ul><li> <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/static-content.springer.com\/esm\/art%3A10.1186%2F1471-2164-13-462\/MediaObjects\/12864_2012_4188_MOESM1_ESM.tiff\" target=\"_blank\">12864_2012_4188_MOESM1_ESM.tiff<\/a> Authors\u2019 original file for figure 1<\/li>\n<li> <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/static-content.springer.com\/esm\/art%3A10.1186%2F1471-2164-13-462\/MediaObjects\/12864_2012_4188_MOESM2_ESM.tiff\" target=\"_blank\">12864_2012_4188_MOESM2_ESM.tiff<\/a> Authors\u2019 original file for figure 2<\/li>\n<li> <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/static-content.springer.com\/esm\/art%3A10.1186%2F1471-2164-13-462\/MediaObjects\/12864_2012_4188_MOESM3_ESM.tiff\" target=\"_blank\">12864_2012_4188_MOESM3_ESM.tiff<\/a> Authors\u2019 original file for figure 3<\/li>\n<li> <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/static-content.springer.com\/esm\/art%3A10.1186%2F1471-2164-13-462\/MediaObjects\/12864_2012_4188_MOESM4_ESM.tiff\" target=\"_blank\">12864_2012_4188_MOESM4_ESM.tiff<\/a> Authors\u2019 original file for figure 4<\/li><\/ul>\n<h3><span class=\"mw-headline\" id=\"Competing_interests\">Competing interests<\/span><\/h3>\n<p>The authors declare that they have no competing interest.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Authors.E2.80.99_contributions\">Authors\u2019 contributions<\/span><\/h3>\n<p>JM and CK conceived and designed the project. JM, FE, GS, CN, NA implemented NG6 pipelines and web site. JM and ST packaged NG6 into a virtual machine. JM and CK drafted the manuscript. All authors read and approved the final manuscript.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<ol class=\"references\">\n<li id=\"cite_note-GlennField11-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-GlennField11_1-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Glenn, T.C. 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(2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2881353\" target=\"_blank\">\"Ergatis: A web interface and scalable software system for bioinformatics workflows\"<\/a>. <i>Bioinformatics<\/i> <b>26<\/b> (12): 1488-1492. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fbioinformatics%2Fbtq167\" target=\"_blank\">10.1093\/bioinformatics\/btq167<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2881353\/\" target=\"_blank\">PMC2881353<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20413634\" target=\"_blank\">20413634<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2881353\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2881353<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Ergatis%3A+A+web+interface+and+scalable+software+system+for+bioinformatics+workflows&rft.jtitle=Bioinformatics&rft.aulast=Orvis%2C+J.%3B+Crabtree%2C+J.%3B+Galens%2C+K.+et+al.&rft.au=Orvis%2C+J.%3B+Crabtree%2C+J.%3B+Galens%2C+K.+et+al.&rft.date=2010&rft.volume=26&rft.issue=12&rft.pages=1488-1492&rft_id=info:doi\/10.1093%2Fbioinformatics%2Fbtq167&rft_id=info:pmc\/PMC2881353&rft_id=info:pmid\/20413634&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2881353&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-TYPO3Home-6\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-TYPO3Home_6-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/typo3.org\/\" target=\"_blank\">\"TYPO3\"<\/a>. 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Marcel Martin<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/cutadapt.readthedocs.org\/en\/stable\/\" target=\"_blank\">https:\/\/cutadapt.readthedocs.org\/en\/stable\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Cutadapt&rft.atitle=&rft.pub=Marcel+Martin&rft_id=https%3A%2F%2Fcutadapt.readthedocs.org%2Fen%2Fstable%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LiFastShort09-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-LiFastShort09_12-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Li, H.; Durbin, R. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2705234\" target=\"_blank\">\"Fast and accurate short read alignment with Burrows\u2013Wheeler transform\"<\/a>. <i>Bioinformatics<\/i> <b>25<\/b> (14): 1754\u201360. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fbioinformatics%2Fbtp324\" target=\"_blank\">10.1093\/bioinformatics\/btp324<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2705234\/\" target=\"_blank\">PMC2705234<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19451168\" target=\"_blank\">19451168<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2705234\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2705234<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Fast+and+accurate+short+read+alignment+with+Burrows%E2%80%93Wheeler+transform&rft.jtitle=Bioinformatics&rft.aulast=Li%2C+H.%3B+Durbin%2C+R.&rft.au=Li%2C+H.%3B+Durbin%2C+R.&rft.date=2009&rft.volume=25&rft.issue=14&rft.pages=1754%E2%80%9360&rft_id=info:doi\/10.1093%2Fbioinformatics%2Fbtp324&rft_id=info:pmc\/PMC2705234&rft_id=info:pmid\/19451168&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2705234&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LiFastLong10-13\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-LiFastLong10_13-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Li, H.; Durbin, R. (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2828108\" target=\"_blank\">\"Fast and accurate long-read alignment with Burrows\u2013Wheeler transform\"<\/a>. <i>Bioinformatics<\/i> <b>26<\/b> (5): 589-95. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fbioinformatics%2Fbtp698\" target=\"_blank\">10.1093\/bioinformatics\/btp698<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2828108\/\" target=\"_blank\">PMC2828108<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20080505\" target=\"_blank\">20080505<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2828108\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2828108<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Fast+and+accurate+long-read+alignment+with+Burrows%E2%80%93Wheeler+transform&rft.jtitle=Bioinformatics&rft.aulast=Li%2C+H.%3B+Durbin%2C+R.&rft.au=Li%2C+H.%3B+Durbin%2C+R.&rft.date=2010&rft.volume=26&rft.issue=5&rft.pages=589-95&rft_id=info:doi\/10.1093%2Fbioinformatics%2Fbtp698&rft_id=info:pmc\/PMC2828108&rft_id=info:pmid\/20080505&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2828108&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-FastQCHome-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-FastQCHome_14-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.bioinformatics.bbsrc.ac.uk\/projects\/fastqc\/\" target=\"_blank\">\"FastQC\"<\/a>. Babraham Bioinformatics<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.bioinformatics.bbsrc.ac.uk\/projects\/fastqc\/\" target=\"_blank\">http:\/\/www.bioinformatics.bbsrc.ac.uk\/projects\/fastqc\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=FastQC&rft.atitle=&rft.pub=Babraham+Bioinformatics&rft_id=http%3A%2F%2Fwww.bioinformatics.bbsrc.ac.uk%2Fprojects%2Ffastqc%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LiTheSeq09-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-LiTheSeq09_15-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Li, H.; Handsaker, B.; Wysoker, A. et al. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2723002\" target=\"_blank\">\"The Sequence Alignment\/Map format and SAMtools\"<\/a>. <i>Bioinformatics<\/i> <b>25<\/b> (16): 2078-9. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fbioinformatics%2Fbtp352\" target=\"_blank\">10.1093\/bioinformatics\/btp352<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2723002\/\" target=\"_blank\">PMC2723002<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19505943\" target=\"_blank\">19505943<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2723002\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2723002<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Sequence+Alignment%2FMap+format+and+SAMtools&rft.jtitle=Bioinformatics&rft.aulast=Li%2C+H.%3B+Handsaker%2C+B.%3B+Wysoker%2C+A.+et+al.&rft.au=Li%2C+H.%3B+Handsaker%2C+B.%3B+Wysoker%2C+A.+et+al.&rft.date=2009&rft.volume=25&rft.issue=16&rft.pages=2078-9&rft_id=info:doi\/10.1093%2Fbioinformatics%2Fbtp352&rft_id=info:pmc\/PMC2723002&rft_id=info:pmid\/19505943&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2723002&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SchlossOpen09-16\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SchlossOpen09_16-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Schloss, P.D.; Westcott, S.L.; Ryabin, T. et al. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2786419\" target=\"_blank\">\"Open-source, platform-independent, community-supported software for describing and comparing microbial communities\"<\/a>. <i>Applied and Environmental Microbiology<\/i> <b>75<\/b> (23): 7537\u20137541. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1128%2FAEM.01541-09\" target=\"_blank\">10.1128\/AEM.01541-09<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2786419\/\" target=\"_blank\">PMC2786419<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19801464\" target=\"_blank\">19801464<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2786419\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2786419<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Open-source%2C+platform-independent%2C+community-supported+software+for+describing+and+comparing+microbial+communities&rft.jtitle=Applied+and+Environmental+Microbiology&rft.aulast=Schloss%2C+P.D.%3B+Westcott%2C+S.L.%3B+Ryabin%2C+T.+et+al.&rft.au=Schloss%2C+P.D.%3B+Westcott%2C+S.L.%3B+Ryabin%2C+T.+et+al.&rft.date=2009&rft.volume=75&rft.issue=23&rft.pages=7537%E2%80%937541&rft_id=info:doi\/10.1128%2FAEM.01541-09&rft_id=info:pmc\/PMC2786419&rft_id=info:pmid\/19801464&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2786419&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-sffHome-17\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-sffHome_17-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/bioinf.comav.upv.es\/sff_extract\/\" target=\"_blank\">\"sff_extract\"<\/a>. Institute for Conservation & Improvement of Valencian Agrodiversity<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/bioinf.comav.upv.es\/sff_extract\/\" target=\"_blank\">https:\/\/bioinf.comav.upv.es\/sff_extract\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=sff_extract&rft.atitle=&rft.pub=Institute+for+Conservation+%26+Improvement+of+Valencian+Agrodiversity&rft_id=https%3A%2F%2Fbioinf.comav.upv.es%2Fsff_extract%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SmartyHome-18\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SmartyHome_18-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.smarty.net\/\" target=\"_blank\">\"Smarty Template Engine\"<\/a>. New Digital Group, Inc<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.smarty.net\/\" target=\"_blank\">http:\/\/www.smarty.net\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Smarty+Template+Engine&rft.atitle=&rft.pub=New+Digital+Group%2C+Inc&rft_id=http%3A%2F%2Fwww.smarty.net%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-jQueryHome-19\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-jQueryHome_19-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/jquery.com\/\" target=\"_blank\">\"jQuery - Write less, do more\"<\/a>. The jQuery Foundation<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/jquery.com\/\" target=\"_blank\">http:\/\/jquery.com\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=jQuery+-+Write+less%2C+do+more&rft.atitle=&rft.pub=The+jQuery+Foundation&rft_id=http%3A%2F%2Fjquery.com%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-GenoToulHome-20\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-GenoToulHome_20-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/get.genotoul.fr\/\" target=\"_blank\">\"G\u00e9nome et Transcriptome\"<\/a>. G\u00e9nome et Transcriptome<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/get.genotoul.fr\/\" target=\"_blank\">http:\/\/get.genotoul.fr\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=G%C3%A9nome+et+Transcriptome&rft.atitle=&rft.pub=G%C3%A9nome+et+Transcriptome&rft_id=http%3A%2F%2Fget.genotoul.fr%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-TrapnellTop09-21\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-TrapnellTop09_21-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Trapnell, C.; Pachter, L.; Salzberg, S.L. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2672628\" target=\"_blank\">\"TopHat: Discovering splice junctions with RNA-Seq\"<\/a>. <i>Bioinformatics<\/i> <b>25<\/b> (9): 1105\u20131111. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fbioinformatics%2Fbtp120\" target=\"_blank\">10.1093\/bioinformatics\/btp120<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2672628\/\" target=\"_blank\">PMC2672628<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19289445\" target=\"_blank\">19289445<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2672628\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2672628<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=TopHat%3A+Discovering+splice+junctions+with+RNA-Seq&rft.jtitle=Bioinformatics&rft.aulast=Trapnell%2C+C.%3B+Pachter%2C+L.%3B+Salzberg%2C+S.L.&rft.au=Trapnell%2C+C.%3B+Pachter%2C+L.%3B+Salzberg%2C+S.L.&rft.date=2009&rft.volume=25&rft.issue=9&rft.pages=1105%E2%80%931111&rft_id=info:doi\/10.1093%2Fbioinformatics%2Fbtp120&rft_id=info:pmc\/PMC2672628&rft_id=info:pmid\/19289445&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2672628&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-RobertsIdent11-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-RobertsIdent11_22-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Roberts, A.; Pimentel, H.; Trapnell, C.; Pachter, L. (2011). \"dentification of novel transcripts in annotated genomes using RNA-Seq\". <i>Bioinformatics<\/i> <b>27<\/b> (17): 2325\u20132329. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fbioinformatics%2Fbtr355\" target=\"_blank\">10.1093\/bioinformatics\/btr355<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21697122\" target=\"_blank\">21697122<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=dentification+of+novel+transcripts+in+annotated+genomes+using+RNA-Seq&rft.jtitle=Bioinformatics&rft.aulast=Roberts%2C+A.%3B+Pimentel%2C+H.%3B+Trapnell%2C+C.%3B+Pachter%2C+L.&rft.au=Roberts%2C+A.%3B+Pimentel%2C+H.%3B+Trapnell%2C+C.%3B+Pachter%2C+L.&rft.date=2011&rft.volume=27&rft.issue=17&rft.pages=2325%E2%80%932329&rft_id=info:doi\/10.1093%2Fbioinformatics%2Fbtr355&rft_id=info:pmid\/21697122&rfr_id=info:sid\/en.wikipedia.org:Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. In several cases, the old URL was dead, and a new functioning URL replaced it. Additionally, numerous proper nouns were not capitalized originally but have been updated in this text. Finally, Ys and Ns have been substituted in the tables for checkmarks and Xs, respectively.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192203\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.537 seconds\nReal time usage: 0.567 seconds\nPreprocessor visited node count: 17567\/1000000\nPreprocessor generated node count: 32113\/1000000\nPost\u2010expand include size: 134236\/2097152 bytes\nTemplate argument size: 40493\/2097152 bytes\nHighest expansion depth: 18\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 528.835 1 - -total\n 83.50% 441.570 1 - Template:Reflist\n 72.97% 385.891 22 - Template:Citation\/core\n 54.11% 286.155 13 - Template:Cite_journal\n 23.09% 122.083 9 - Template:Cite_web\n 11.66% 61.685 1 - Template:Infobox_journal_article\n 11.22% 59.312 1 - Template:Infobox\n 9.57% 50.586 36 - Template:Citation\/identifier\n 6.70% 35.430 80 - Template:Infobox\/row\n 4.17% 22.063 22 - Template:Citation\/make_link\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:8474-0!*!0!!en!5!* and timestamp 20181214192203 and revision id 24768\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment\">https:\/\/www.limswiki.org\/index.php\/Journal:NG6:_Integrated_next_generation_sequencing_storage_and_processing_environment<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","49a52cbdf428fd81f28d257904a1dc05_images":["https:\/\/www.limswiki.org\/images\/2\/2f\/Fig1_Mariette_BMCGenomics2015_13.jpg","https:\/\/www.limswiki.org\/images\/1\/1d\/Fig2_Mariette_BMCGenomics2015_13.jpg","https:\/\/www.limswiki.org\/images\/0\/0a\/Fig3_Mariette_BMCGenomics2015_13.jpg","https:\/\/www.limswiki.org\/images\/e\/eb\/Fig4_Mariette_BMCGenomics2015_13.jpg"],"49a52cbdf428fd81f28d257904a1dc05_timestamp":1544815323,"2dc8d868e85040728288505b6c391110_type":"article","2dc8d868e85040728288505b6c391110_title":"MaPSeq, a service-oriented architecture for genomics research within an academic biomedical research institution (Reilly et al. 2015)","2dc8d868e85040728288505b6c391110_url":"https:\/\/www.limswiki.org\/index.php\/Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution","2dc8d868e85040728288505b6c391110_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:MaPSeq, a service-oriented architecture for genomics research within an academic biomedical research institution\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nMaPSeq, a service-oriented architecture for genomics research within an academic biomedical research institutionJournal\n \nInformaticsAuthor(s)\n \nReilly, J.; Ahalt, S.; McGee, J.; Owen, P.; Schmitt, C.; Wilhelmsen, K.Author affiliation(s)\n \nUniversity of North Carolina at Chapel HillPrimary contact\n \nPhone: +1 919-445-9619 (Wilhelmsen)Editors\n \nBryant, A.Year published\n \n2015Volume and issue\n \n2 (3)Page(s)\n \n20\u201330DOI\n \n10.3390\/informatics2030020ISSN\n \n2227-9709Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttp:\/\/www.mdpi.com\/2227-9709\/2\/3\/20\/htmDownload\n \nhttp:\/\/www.mdpi.com\/2227-9709\/2\/3\/20\/pdf (PDF)\n\nContents\n\n1 Abstract \n2 Introduction \n3 Challenges driving the conceptualization and SOA design of MaPSeq \n\n3.1 Challenge 1 \n3.2 Challenge 2 \n3.3 Challenge 3 \n\n\n4 Existing solutions \n5 MaPSeq technical architecture and capabilities \n\n5.1 Overview of MaPSeq architecture \n5.2 MaPSeq pipelines \n5.3 HTCondor \n5.4 GATE \n5.5 Security, interfaces, and administration \n\n\n6 Discussion \n\n6.1 Limitations \n\n\n7 Conclusions \n8 Acknowledgements \n9 Author contributions \n10 Conflicts of interest \n11 References \n12 Notes \n\n\n\nAbstract \nGenomics research presents technical, computational, and analytical challenges that are well recognized. Less recognized are the complex sociological, psychological, cultural, and political challenges that arise when genomics research takes place within a large, decentralized academic institution. In this paper, we describe a Service-Oriented Architecture (SOA) \u2014 MaPSeq \u2014 that was conceptualized and designed to meet the diverse and evolving computational workflow needs of genomics researchers at our large, hospital-affiliated, academic research institution. We present the institutional challenges that motivated the design of MaPSeq before describing the architecture and functionality of MaPSeq. We then discuss SOA solutions and conclude that approaches such as MaPSeq enable efficient and effective computational workflow execution for genomics research and for any type of academic biomedical research that requires complex, computationally-intense workflows. \nKeywords: service-oriented architecture; genomics; massively parallel sequencing; computational workflow; academic biomedical research; decentralized organization; distributed decision-making\n\nIntroduction \nGenomics research presents well-recognized technical, computational, and analytical challenges.[1][2][3][4] For example, while the technology for massively parallel genomic sequencing has progressed to the point where large amounts of data can be generated at a rapid pace and for a reasonable cost, the analytical burden presented by this massive amount of data can quickly overwhelm the genomic analyst. Indeed, the analysis and interpretation of genetic findings is generally considered the rate-limiting step in the translation of genomic sequencing data into clinical practice and patient care.[4]\nLess recognized challenges to research in genomics and any biomedical field are the sociological, psychological, cultural, and political barriers, many of which arise from the organizational structure within which the research takes place. Indeed, research organizations tend to fall somewhere on a continuum between completely centralized and completely decentralized.[5][6][7][8] Each of these extremes has advantages and disadvantages. Centralized organizations traditionally function within a simple organizational design, with singular decision-making, top-level operational control, a consolidated budget, strong\/clear communication channels, uniform culture and politics, and a high degree of efficiency, but at the expense of flexibility. Decentralized organizations, in contrast, generally operate within a complex organizational design, with distributed decision-making, local operational control, regionalized budgets, numerous weak or broken communication channels, inconsistent (and sometimes conflicting) culture and politics, and a high degree of flexibility, but at the expense of efficiency. The conceptualization, design, development, and implementation of information technology (IT) solutions for research in genomics and any biomedical field must therefore involve careful consideration of not only the needs of the user base, but also the organizational structure within which the research takes place.\nHerein, we present a Service-Oriented Architecture (SOA) application \u2014 termed MaPSeq \u2014 that was conceptualized and designed to address the organizational challenges of computation-intensive biomedical research within a decentralized academic institution. In this article, we first describe the challenges that contributed to the conceptualization and design of MaPSeq. We then provide an overview of the technical architecture and capabilities of MaPSeq. Finally, we provide a discussion of service-oriented solutions such as MaPSeq.\n\nChallenges driving the conceptualization and SOA design of MaPSeq \nThe design of MaPSeq was motivated by challenges that arose during the implementation of a genomic sequencing project titled \u201cNorth Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing\u201d (NCGENES). This project, which is funded by the National Human Genome Resource Institute, aims to conduct whole exome sequencing of 500 patient samples drawn from multiple disease categories. NCGENES is a complex project, with both research and clinical arms. Soon after the project was initiated, the research and clinical teams realized that there were numerous barriers and roadblocks that needed to be overcome in order to achieve the analytical goals of the project. (See Table 1 for overview.)\n\n\n\n\n\n\n\nTable 1. An overview of the challenges that contributed to the architectural design of MaPSeq\n\n\nChallenge\n\nDescription\n\nMaPSeq SOA Solution\n\nBenefits\n\n\nChallenge 1\n\nDiverse and evolving computational workflow needs; expanding complexity of workflows\n\nDifferent services designed to address different needs\n\nFlexibility; scalability; extensibility\n\n\nChallenge 2\n\nSilos of distributed, uncoordinated compute resources; network idiosyncrasies\n\nOpportunistic use of distributed compute resources without need for a cloud-based software stack\n\nInteroperability; extensibility; generalizability\n\n\nChallenge 3\n\nPolitical and cultural resistance to change; human roadblocks in the automation of workflow pipelines\n\nReusable automated attributes to gradually replace human workflow processes\n\nAchievability; accessibility; functionality\n\n\n\nChallenge 1 \nAcademic institutions face the challenge of balancing the needs of large, funded, research projects that typically support the development of an informatics infrastructure with the needs of smaller, often unfunded, research projects that cannot afford significant development costs. Furthermore, few research projects are sufficiently funded to support future development needs. Our institution faced these challenges when trying to balance the needs of the NCGENES investigative team with those of other investigative teams and anticipate future needs. The scale, general applicability, and complexity of massively parallel sequencing favored the development of an SOA approach to support both current and future needs related to genomic and non-genomic computationally-intense serial workflows.\n\nChallenge 2 \nAs is typical for an academic institution, our genomics infrastructure developed in an ad hoc manner, with multiple investigative teams working independently across the university campus. The result was a burgeoning, uncoordinated cluster of distributed compute resources. Compounding this challenge were the numerous network idiosyncrasies that prevented administrators within one network from accessing compute resources within a different network; thus, access privileges to campus compute resources were determined locally and required on-site (rather than remote) access.\n\nChallenge 3 \nDecision-making at large academic institutions tends to be decentralized, with numerous decision makers enforcing different (and often conflicting) policies and procedures. This organizational structure inevitably leads to political and cultural conflicts and resistance to change, particularly when \u201cexternal\u201d IT teams attempt to change the processes in place among \u201ccentral\u201d investigative teams. Political and cultural resistance to the NCGENES project was encountered early on as the investigative team identified many barriers to the automation of human user-controlled workflow processes. While the existing human user-run workflows met the needs of small genomic sequencing projects and user groups, these workflows were inefficient for the computationally-demanding, whole-exome sequencing needs of NCGENES. Moreover, the use of a human contact as the point of access to an existing workflow created a roadblock to the execution of NCGENES, reduced the efficiency of genomic analysis, and threatened the security of sensitive patient data.\n\nExisting solutions \nNumerous Workflow Management Systems and workflow pipelines for genomic analysis exist, including COSMOS[9], Ergatis[10], i2b2[11], LONI[12], NG6[13], NGSANE[14], Orione[15], RUbioSeq[16], SeqInCloud[17], STATegra EMS[18], TREVA[19], and Pegasus.[20] Our team evaluated each of these systems for their ability to overcome the challenges described above. We found that existing solutions could address some, but not all, of the roadblocks and barriers that were hindering progress on the NCGENES project and that a new solution was needed. While all of the existing workflow systems and pipelines have proven to be effective, each has limitations.[21] MaPSeq is not unique in this regard, but it is responsive to the key features of a decentralized research organization. Specifically, as an SOA, MaPSeq allows for integration with multiple clients and distributed systems, whether local, open source, or commercial, and provides tailored, reusable, automated service solutions that address the varying and evolving needs and preferences of decentralized decision-makers. MaPSeq is scalable and can support both small- and large-scale projects and thus is responsive to the computational needs of all investigators. MaPSeq is efficient and allows for seamless, opportunistic use of distributed compute resources. Finally, the service-oriented, automated approach requires little coordination or communication among individual user groups and thus avoids local nuances in politics and culture. \n\nMaPSeq technical architecture and capabilities \nOverview of MaPSeq architecture \nMaPSeq was designed as an open source, plugin-based SOA solution[22][23][24] that provides modifiable services to make opportunistic use of multiple institutional and cloud-based compute resources in order to efficiently complete the multitude of steps involved in the analysis of large-scale, genomic sequencing data (see Figure 1). The plugin framework of MaPSeq is based on the Open Services Gateway initiative (OSGi). This framework was chosen because of its modular agile architecture and the ability to remotely manage workflow pipelines in an on-demand manner and within a sandboxed environment. Moreover, the investigative team had relevant prior experience with the Open Science Grid Engagement Program, which aims to facilitate collaborative research through advanced distributed computing technologies.\nMaPSeq and, its sister technology, the Grid Access Triage Engine (GATE), are built on top of ApacheTM Karaf, which is an OSGi-based lightweight container for application deployment. MapSeq works together with GATE to provide extensible capabilities for the analysis of genomic sequencing data, including: pipeline execution and management; meta-scheduling of workflow jobs; opportunistic compute-node utilization and management; secure messaging and data transfer; and client access via web services.\n\n\n\n\n\n\n\n\n\n Figure 1. An overview of the MaPSeq architecture\n\n\n\nMaPSeq pipelines \nMaPSeq pipelines (Figure 1) are OSGi-based plugins comprised of a number of bundles and\/or services. At a minimum, a MaPSeq pipeline consists of: (1) a Java Message Service destination that exposes a mechanism whereby a user can trigger a pipeline; (2) a workflow designed as a Directed Acyclic Graph (DAG) and consisting of a collection of programmatic tasks; (3) an executor that dequeues the workflows at a customizable frequency (e.g., two workflows every five minutes, ten workflows every three minutes, etc.); and (4) a metadata file that describes all of the aforementioned features and tracks their status. Complex pipelines can be broken into numerous smaller sub-pipelines to enable symbolic check-pointing or fault tolerance. For example, a genomic analysis pipeline can be logically split into two sub-pipelines: an alignment sub-pipeline and a variant calling sub-pipeline. This approach enables a researcher to, for example, modify a step in the variant calling sub-pipeline and re-run that sub-pipeline without the need to re-run the alignment sub-pipeline, thereby reducing the runtime burden. Additionally, this approach allows the sub-pipelines to be reused in other pipelines, thus fostering software re-usability. Of note, all pipelines are project-specific and defined by the needs of the project and research team such that pipeline development is tailored to a specific application.\n\nHTCondor \nHTCondor (Figure 1) serves as a central manager and provides meta-scheduling for MaPSeq via the DAG Manager (DAGMan). MaPSeq workflows are comprised of numerous modules that form the vertices of a DAG. The DAGs can be exported for submission to HTCondor using DAGMan. MaPSeq provides a suite of modules that wrap third-party libraries (e.g., GATK, Picard, etc.) for execution on the grid and that include a number of lifecycle events. These lifecycle events check for valid inputs and outputs, successful execution, and provenance of job metadata, thus ensuring consistency and rapid detection of errors. HTCondor manages serial execution of MaPSeq modules, as well as job-to-machine resource negotiation or \u201cmatchmaking\u201d. The matchmaking process identifies job requirements (e.g., four cores and 4 GB memory required), as defined by the job metadata, and pairs those requirements with available machine attributes (e.g., eight cores and 32 GB memory available). After a MaPSeq module is executed, that module, or job wrapper, persists the job metadata over web services into a PostgreSQL database. HTCondor Glideins are used to provision compute resources for the execution of jobs, as described below.\n\nGATE \nGATE (Figure 1) is a homegrown OSGi-based system that serves as a sister technology for MaPSeq. Whereas MaPSeq uses plugins to execute workflow pipelines, GATE uses plugins to access compute resources. GATE continuously monitors a local HTCondor instance for idle jobs and profiles compute resources for availability. If an idle job is detected, then GATE uses plugins to submit an HTCondor Glidein to the most appropriate compute resource, which then joins the local HTCondor pool. GATE defers matchmaking to the HTCondor Negotiator, which uses daemons to perform the matchmaking. GATE grows and shrinks the number of Glideins by assessing the number of running and idle local jobs against the number of running and idle Glidein jobs on the compute resource grid. After a Glidein is activated, it registers back to the HTCondor Central Manager as an available resource. This approach enables jobs to be both site-specific and site-agnostic.\n\nSecurity, interfaces, and administration \nOf significance, both MaPSeq and GATE use Secure SHell (SSH) technology, running with daemons, for authentication and data transfer. This level of security is particularly important for applications such as genomics that involve the movement of sensitive patient data.\nClients can interface with MaPSeq using Apache\u2122 CXF (Figure 1), which is an industry-standard web service. Both Simple Object Access Protocol (SOAP) and Representational State Transfer (RESTful) services are supported by Apache CXF. Pipeline invocations are triggered via a JavaScript Object Notation (JSON)-formatted message to an ApacheTM ActiveMQ destination. The JSON message contains the mapping between a MaPSeq-managed sample file instance and a workflow run instance. A pipeline-specific \u201cmessage listener\u201d then determines if the message is legitimate for subsequent processing. For genomic sequencing data, this process may involve verification that an object layer in the data file specifies that the data file contains raw sequencing data and sufficient metadata. A rich set of MaPSeq reports can be generated and sent to a client via email, for review and detection of potential problems (see example in Figure 2).\nApache Karaf is unique among containers in that it embeds an SSH daemon to enable a client to administratively manage pipeline deployment within a sandboxed environment. MaPSeq pipelines can be added, removed, or altered without having to stop the container, thereby provisioning a continuous, uninterrupted environment to execute new pipelines while existing pipelines are running. This accessibility allows for a pipeline developer to independently iterate on pipeline improvements.\n\n\n\n\n\n\n\n\n\n Figure 2. An example of a MaPSeq output log showing the duration of a job (total and average minutes (min) over a one-week time period) by specific task\n\n\n\nDiscussion \nGenomics research within an academic environment presents numerous challenges. In addition to the computational and technical challenges inherent in genomics research[1][2][3][4], there are complex sociological, psychological, cultural, and political challenges that affect operations within academic institutions and indeed many other types of organizations.[25][26][27][28][29] Moreover, academic biomedical research institutions tend to be decentralized in their organizational structure. Whereas centralized organizations tend to function within a simple organizational design, with singular decision-making, top-level operational control, a consolidated budget, strong\/clear communication channels, uniform culture and politics, and a high degree of operational efficiency, decentralized organizations, in contrast, operate within a complex organizational design, with distributed decision-making, localized operations and budgets, weak communication channels, nuances in culture and politics across academic units, and minimal operational efficiency.[5][6][7][8]\nMaPSeq provides a reusable, service-oriented solution that addresses the diverse and evolving computational needs of decentralized decision-makers and scales to support both small- and large-scale projects. The automated approach requires little coordination or communication among individual user groups and thus avoids human roadblocks that may otherwise decrease efficiency. By leveraging the OSGi framework and Apache Karaf, MaPSeq allows for quick development iterations on MaPSeq pipeline plugins; pipelines can be created, altered, deployed, triggered, and removed without having to stop and restart the container. Finally, the use of HTCondor as a meta-scheduler and the addition of GATE as a sister technology allow MaPSeq to extend compute cluster capacity and make opportunistic use of distributed compute resources across the university campus.\nIn an environment of legacy systems, distributed and uncoordinated decision-making and compute resources, diverse and evolving user needs, and political and cultural resistance to change, centralized technical solutions will not promote efficient and effective biomedical research. SOA solutions provide the flexibility, scalability, extensibility, accessibility, interoperability, generalizability, achievability, and functionality required to attain efficient and effective, transformative biomedical research within a decentralized organization.\n\nLimitations \nLike any scientific workflow pipeline, MaPSeq is not without limitations.[21] First, while the underlying technology is open source and freely available, there is a considerable learning curve involved in implementation of the technology. Second, GATE is a homegrown solution and requires institution-specific adaptation before it can be adopted for use. Third, the MaPSeq solution must be continuously assessed against the evolving needs of relevant stakeholders, including users, patients, investigators, institutional administrators, and policy makers.\n\nConclusions \nSOA solutions such as MaPSeq are well suited to overcome the many challenges to biomedical research that are inherent in a decentralized academic institution. MaPSeq has transformed genomics research at our institution and currently supports several large genomics research projects, as well as a few small ones. While MaPSeq was originally termed as an acronym for \u201cMassively Parallel Sequencing\u201d and designed to support genomics research, we note that the general architecture and approach can be adapted for other complex or computationally-intense workflows.\nFinally, we note that MaPSeq (version 5.0) is available through a University of North Carolina Open Source Public License (version 1.1, \u00a92004). The only prerequisites are Java 1.7+, Apache\u2122 Maven 3, and a network connection (full technical specifications and installation\/operational instructions can be found at[30], with an accompanying RENCI technical report at reference[31]).\n\nAcknowledgements \nThis project was conceptualized and implemented by RENCI and the UNC High-Throughput Sequencing Facility, in collaboration with Information Technology Services Research Computing and the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill and with funding from the National Institutes of Health (1R01-DA030976-01, 1U01-HG006487-01, 5UL1-RR025747-03, 1U19-HD077632-01, and 1U01-HG007437-01). The authors acknowledge the contributions of Corbin Jones, Associate Professor in the Department of Biology, and Jeff Roach, Senior Scientific Research Associate for Research Computing, Information Technology Services, University of North Carolina at Chapel Hill, to the design and implementation of MaPSeq. Karamarie Fecho, provided writing support for this manuscript, and RENCI provided funding for that support.\n\nAuthor contributions \nJason Reilly designed and implemented MaPSeq with assistance from Phillips Owen as a replacement of earlier work by Charles Schmitt and based on prior work by John McGee, Kirk Wilhelmsen oversaw the implementation of MapSeq. Stanley Ahalt provided general guidance and facilities support for the development and implementation of MaPSeq.\n\nConflicts of interest \nThe authors declare no conflict of interest.\n\nReferences \n\n\n\u2191 1.0 1.1 Koboldt, D.C.; Ding, L.; Mardis, E.R.; Wilson, R.K. (2010). \"Challenges of sequencing human genomes\". 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(2011). \"A translational engine at the national scale: Informatics for integrating biology and the bedside\". Journal of the American Medical Informatics Association 19 (2): 181-185. doi:10.1136\/amiajnl-2011-000492. PMC PMC3277623. PMID 22081225. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3277623 .   \n\n\u2191 Dinov, I.D.; Torri, F.; Macciardi, F. et al. (2011). \"Applications of the pipeline environment for visual informatics and genomics computations\". BMC Bioinformatics 12: 304. doi:10.1186\/1471-2105-12-304. PMC PMC3199760. PMID 21791102. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3199760 .   \n\n\u2191 Mariette, J.; Escudi\u00e9, F.; Allias, N. et al. (2012). \"Integrated next generation sequencing storage and processing environment\". BMC Genomics 13: 462. doi:10.1186\/1471-2164-13-462. PMC PMC3444930. PMID 22958229. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3444930 .   \n\n\u2191 Buske, F.A.; French, H.J.; Smith, M.A. et al. (2014). \"NGSANE: A lightweight production informatics framework for high-throuput data analysis\". Bioinformatics 30 (10): 1471-1472. doi:10.1093\/bioinformatics\/btu036. PMC PMC4016703. PMID 24470576. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4016703 .   \n\n\u2191 Cuccuru, G.; Orsini, M.; Pinna, A. et al. (2014). \"Orione, a web-based framework for NGS analysis in microbiology\". Bioinformatics 30 (13): 1928-1929. doi:10.1093\/bioinformatics\/btu135. PMC PMC4071203. PMID 24618473. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4071203 .   \n\n\u2191 Rubio-Camarillo, M.; G\u00f3mex-L\u00f3pez, G.; Fern\u00e1ndez, J.M. et al. (2013). \"RUbioSeq: A suite of parallelized pipelines to automate exome variation and bisulfite-seq analyses\". Bioinformatics 29 (13): 1687-1689. doi:10.1093\/bioinformatics\/btt203. PMC PMC3694642. PMID 23630175. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3694642 .   \n\n\u2191 Mohamed, N.M.; Lin, H.; Feng, W.C. (2013). \"Accelerating Data-Intensive Genome Analysis in the Cloud\" (PDF). Virginia Tech. http:\/\/synergy.cs.vt.edu\/pubs\/papers\/nabeel-bicob13-genome-analysis-cloud.pdf . Retrieved 16 April 2015 .   \n\n\u2191 De Diego, R.H.; Boix-Chova, N.; G\u00f3mez-Cabrero, D. et al. (2014). \"STATegra EMS: An experiment management system for complex next-generation omics experiments\". BMC Systems Biology 8 (Suppl 2): S9. doi:10.1186\/1752-0509-8-S2-S9. PMC PMC4101697. PMID 25033091. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4101697 .   \n\n\u2191 Li, J.; Doyle, M.A.; Saeed, I. et al. (2014). \"Bioinformatics pipelines for targeted resequencing and whole-exome sequencing of human and mouse genomes: A virtual appliance approach for instant deployment\". PLOS ONE 9 (4): e95217. doi:10.1371\/journal.pone.0095217. PMC PMC3994043. PMID 24752294. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3994043 .   \n\n\u2191 Deelman, E.; Vahi, K.; Juve, G. et al. (2015). \"Pegasus: A workflow management system for science automation\". Future Generation Computer Systems 46 (5): 17\u201335. doi:10.1016\/j.future.2014.10.008.   \n\n\u2191 21.0 21.1 Bromberg, Y. (2013). \"Building a genome analysis pipeline to predict disease risk and prevent disease\". Journal of Molecular Biology 425 (21): 3993\u20134005. doi:10.1016\/j.jmb.2013.07.038. PMID 23928561.   \n\n\u2191 Sprott, D.; Wilkes, L. (January 2004). \"Understanding Service-Oriented Architecture\". Microsoft Developer Network. Microsoft. https:\/\/msdn.microsoft.com\/en-us\/library\/aa480021.aspx . Retrieved 16 April 2015 .   \n\n\u2191 CIO Staff (19 March 2007). \"SOA Definition and Solutions\". CIO. CXO Media, Inc. http:\/\/www.cio.com\/article\/2439274\/service-oriented-architecture\/soa-definition-and-solutions.html . Retrieved 16 April 2015 .   \n\n\u2191 Bailey, M. (2008). \"Principles of Service Oriented Architecture\". SlidePlayer. SlidePlayer.com, Inc. http:\/\/slideplayer.com\/slide\/701834\/ . Retrieved 16 April 2015 .   \n\n\u2191 Williams, R.; Edge, D. (1996). \"The social shaping of technology\". Research Policy 25 (6): 865\u2013899. doi:10.1016\/0048-7333(96)00885-2.   \n\n\u2191 Lorenzi, N.M.; Riley, R.T.; Blyth, A.J.C. et al. (1997). \"Antecedents of the people and organizational aspects of medical informatics: Review of the literature\". Journal of the American Medical Informatics Association 4 (62): 79-93. doi:10.1136\/jamia.1997.0040079. PMC PMC61497. PMID 9067874. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC61497 .   \n\n\u2191 Jasperson, J.S.; Sambamurthy, V.; Zmud, R.W. (1999). \"Social influence and individual IT use: Unraveling the pathways of appropriation moves\". Proceedings of the 20th International Conference on Information Systems: 113\u2013118. http:\/\/aisel.aisnet.org\/icis1999\/10\/ .   \n\n\u2191 Sassen, S. (2002). \"Towards a sociology of information technology\". Current Sociology 50 (3): 365-388. doi:10.1177\/0011392102050003005.   \n\n\u2191 Schmidt, J.; Lyle, D. (2005). Integration Competency Center: An Implementation Methodology. Redwood City, CA: Informatics Corp. pp. 153. ISBN 9780976916307.   \n\n\u2191 \"Massively Parallel Sequencing\". University of North Carolina at Chapel Hill. 2015. http:\/\/jdr0887.github.io\/MaPSeq-API\/index.html . Retrieved 13 July 2015 .   \n\n\u2191 \"TR-14-03 MaPSeq, A Computational and Analytical Workflow Manager for Downstream Genomic Sequencing\". RENCI. 03 June 2014. http:\/\/renci.org\/technical-reports\/mapseq-computational-and-analytical-workflow-manager\/ . Retrieved 13 July 2015 .   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. 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Less recognized are the complex sociological, psychological, cultural, and political challenges that arise when genomics research takes place within a large, decentralized academic institution. In this paper, we describe a Service-Oriented Architecture (SOA) \u2014 MaPSeq \u2014 that was conceptualized and designed to meet the diverse and evolving computational workflow needs of genomics researchers at our large, <a href=\"https:\/\/www.limswiki.org\/index.php\/Hospital\" title=\"Hospital\" target=\"_blank\" class=\"wiki-link\" data-key=\"b8f070c66d8123fe91063594befebdff\">hospital<\/a>-affiliated, academic research institution. We present the institutional challenges that motivated the design of MaPSeq before describing the architecture and functionality of MaPSeq. We then discuss SOA solutions and conclude that approaches such as MaPSeq enable efficient and effective computational workflow execution for genomics research and for any type of academic biomedical research that requires complex, computationally-intense workflows. \n<\/p><p><b>Keywords<\/b>: service-oriented architecture; genomics; massively parallel sequencing; computational workflow; academic biomedical research; decentralized organization; distributed decision-making\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>Genomics research presents well-recognized technical, computational, and analytical challenges.<sup id=\"rdp-ebb-cite_ref-KoboldtChal10_1-0\" class=\"reference\"><a href=\"#cite_note-KoboldtChal10-1\" rel=\"external_link\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-KahnOn11_2-0\" class=\"reference\"><a href=\"#cite_note-KahnOn11-2\" rel=\"external_link\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-GreenClin14_3-0\" class=\"reference\"><a href=\"#cite_note-GreenClin14-3\" rel=\"external_link\">[3]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-DeweyClin14_4-0\" class=\"reference\"><a href=\"#cite_note-DeweyClin14-4\" rel=\"external_link\">[4]<\/a><\/sup> For example, while the technology for massively parallel genomic <a href=\"https:\/\/www.limswiki.org\/index.php\/Sequencing\" title=\"Sequencing\" class=\"mw-disambig wiki-link\" target=\"_blank\" data-key=\"e36167a9eb152ca16a0c4c4e6d13f323\">sequencing<\/a> has progressed to the point where large amounts of data can be generated at a rapid pace and for a reasonable cost, the analytical burden presented by this massive amount of data can quickly overwhelm the genomic analyst. Indeed, the analysis and interpretation of genetic findings is generally considered the rate-limiting step in the translation of genomic sequencing data into clinical practice and patient care.<sup id=\"rdp-ebb-cite_ref-DeweyClin14_4-1\" class=\"reference\"><a href=\"#cite_note-DeweyClin14-4\" rel=\"external_link\">[4]<\/a><\/sup>\n<\/p><p>Less recognized challenges to research in genomics and any biomedical field are the sociological, psychological, cultural, and political barriers, many of which arise from the organizational structure within which the research takes place. Indeed, research organizations tend to fall somewhere on a continuum between completely centralized and completely decentralized.<sup id=\"rdp-ebb-cite_ref-OrlikowskiTech01_5-0\" class=\"reference\"><a href=\"#cite_note-OrlikowskiTech01-5\" rel=\"external_link\">[5]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-HeidenCent07_6-0\" class=\"reference\"><a href=\"#cite_note-HeidenCent07-6\" rel=\"external_link\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-JainToCent13_7-0\" class=\"reference\"><a href=\"#cite_note-JainToCent13-7\" rel=\"external_link\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-IngramCent15_8-0\" class=\"reference\"><a href=\"#cite_note-IngramCent15-8\" rel=\"external_link\">[8]<\/a><\/sup> Each of these extremes has advantages and disadvantages. Centralized organizations traditionally function within a simple organizational design, with singular decision-making, top-level operational control, a consolidated budget, strong\/clear communication channels, uniform culture and politics, and a high degree of efficiency, but at the expense of flexibility. Decentralized organizations, in contrast, generally operate within a complex organizational design, with distributed decision-making, local operational control, regionalized budgets, numerous weak or broken communication channels, inconsistent (and sometimes conflicting) culture and politics, and a high degree of flexibility, but at the expense of efficiency. The conceptualization, design, development, and implementation of information technology (IT) solutions for research in genomics and any biomedical field must therefore involve careful consideration of not only the needs of the user base, but also the organizational structure within which the research takes place.\n<\/p><p>Herein, we present a Service-Oriented Architecture (SOA) application \u2014 termed MaPSeq \u2014 that was conceptualized and designed to address the organizational challenges of computation-intensive biomedical research within a decentralized academic institution. In this article, we first describe the challenges that contributed to the conceptualization and design of MaPSeq. We then provide an overview of the technical architecture and capabilities of MaPSeq. Finally, we provide a discussion of service-oriented solutions such as MaPSeq.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Challenges_driving_the_conceptualization_and_SOA_design_of_MaPSeq\">Challenges driving the conceptualization and SOA design of MaPSeq<\/span><\/h2>\n<p>The design of MaPSeq was motivated by challenges that arose during the implementation of a genomic sequencing project titled \u201cNorth Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing\u201d (NCGENES). This project, which is funded by the National Human Genome Resource Institute, aims to conduct whole exome sequencing of 500 patient samples drawn from multiple disease categories. NCGENES is a complex project, with both research and clinical arms. Soon after the project was initiated, the research and clinical teams realized that there were numerous barriers and roadblocks that needed to be overcome in order to achieve the analytical goals of the project. (See Table 1 for overview.)\n<\/p>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\" colspan=\"4\"><b>Table 1.<\/b> An overview of the challenges that contributed to the architectural design of MaPSeq\n<\/td><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">Challenge\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Description\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">MaPSeq SOA Solution\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Benefits\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Challenge 1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Diverse and evolving computational workflow needs; expanding complexity of workflows\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Different services designed to address different needs\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Flexibility; scalability; extensibility\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Challenge 2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Silos of distributed, uncoordinated compute resources; network idiosyncrasies\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Opportunistic use of distributed compute resources without need for a cloud-based software stack\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Interoperability; extensibility; generalizability\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Challenge 3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Political and cultural resistance to change; human roadblocks in the automation of workflow pipelines\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Reusable automated attributes to gradually replace human workflow processes\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Achievability; accessibility; functionality\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h3><span class=\"mw-headline\" id=\"Challenge_1\">Challenge 1<\/span><\/h3>\n<p>Academic institutions face the challenge of balancing the needs of large, funded, research projects that typically support the development of an <a href=\"https:\/\/www.limswiki.org\/index.php\/Informatics_(academic_field)\" title=\"Informatics (academic field)\" target=\"_blank\" class=\"wiki-link\" data-key=\"0391318826a5d9f9a1a1bcc88394739f\">informatics<\/a> infrastructure with the needs of smaller, often unfunded, research projects that cannot afford significant development costs. Furthermore, few research projects are sufficiently funded to support future development needs. Our institution faced these challenges when trying to balance the needs of the NCGENES investigative team with those of other investigative teams and anticipate future needs. The scale, general applicability, and complexity of massively parallel sequencing favored the development of an SOA approach to support both current and future needs related to genomic and non-genomic computationally-intense serial workflows.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Challenge_2\">Challenge 2<\/span><\/h3>\n<p>As is typical for an academic institution, our genomics infrastructure developed in an <i>ad hoc<\/i> manner, with multiple investigative teams working independently across the university campus. The result was a burgeoning, uncoordinated cluster of distributed compute resources. Compounding this challenge were the numerous network idiosyncrasies that prevented administrators within one network from accessing compute resources within a different network; thus, access privileges to campus compute resources were determined locally and required on-site (rather than remote) access.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Challenge_3\">Challenge 3<\/span><\/h3>\n<p>Decision-making at large academic institutions tends to be decentralized, with numerous decision makers enforcing different (and often conflicting) policies and procedures. This organizational structure inevitably leads to political and cultural conflicts and resistance to change, particularly when \u201cexternal\u201d IT teams attempt to change the processes in place among \u201ccentral\u201d investigative teams. Political and cultural resistance to the NCGENES project was encountered early on as the investigative team identified many barriers to the automation of human user-controlled workflow processes. While the existing human user-run workflows met the needs of small genomic sequencing projects and user groups, these workflows were inefficient for the computationally-demanding, whole-exome sequencing needs of NCGENES. Moreover, the use of a human contact as the point of access to an existing workflow created a roadblock to the execution of NCGENES, reduced the efficiency of genomic analysis, and threatened the security of sensitive patient data.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Existing_solutions\">Existing solutions<\/span><\/h2>\n<p>Numerous Workflow Management Systems and workflow pipelines for genomic analysis exist, including COSMOS<sup id=\"rdp-ebb-cite_ref-GafniCOS14_9-0\" class=\"reference\"><a href=\"#cite_note-GafniCOS14-9\" rel=\"external_link\">[9]<\/a><\/sup>, Ergatis<sup id=\"rdp-ebb-cite_ref-OrvisErg10_10-0\" class=\"reference\"><a href=\"#cite_note-OrvisErg10-10\" rel=\"external_link\">[10]<\/a><\/sup>, i2b2<sup id=\"rdp-ebb-cite_ref-KohaneATrans11_11-0\" class=\"reference\"><a href=\"#cite_note-KohaneATrans11-11\" rel=\"external_link\">[11]<\/a><\/sup>, LONI<sup id=\"rdp-ebb-cite_ref-DinovApp11_12-0\" class=\"reference\"><a href=\"#cite_note-DinovApp11-12\" rel=\"external_link\">[12]<\/a><\/sup>, NG6<sup id=\"rdp-ebb-cite_ref-MarietteInt12_13-0\" class=\"reference\"><a href=\"#cite_note-MarietteInt12-13\" rel=\"external_link\">[13]<\/a><\/sup>, NGSANE<sup id=\"rdp-ebb-cite_ref-BuskeNG14_14-0\" class=\"reference\"><a href=\"#cite_note-BuskeNG14-14\" rel=\"external_link\">[14]<\/a><\/sup>, Orione<sup id=\"rdp-ebb-cite_ref-CuccuruOrione14_15-0\" class=\"reference\"><a href=\"#cite_note-CuccuruOrione14-15\" rel=\"external_link\">[15]<\/a><\/sup>, RUbioSeq<sup id=\"rdp-ebb-cite_ref-Rubio-CamarilloRU13_16-0\" class=\"reference\"><a href=\"#cite_note-Rubio-CamarilloRU13-16\" rel=\"external_link\">[16]<\/a><\/sup>, SeqInCloud<sup id=\"rdp-ebb-cite_ref-MohamedAcc13_17-0\" class=\"reference\"><a href=\"#cite_note-MohamedAcc13-17\" rel=\"external_link\">[17]<\/a><\/sup>, STATegra EMS<sup id=\"rdp-ebb-cite_ref-DeDiegoStat14_18-0\" class=\"reference\"><a href=\"#cite_note-DeDiegoStat14-18\" rel=\"external_link\">[18]<\/a><\/sup>, TREVA<sup id=\"rdp-ebb-cite_ref-LiBio14_19-0\" class=\"reference\"><a href=\"#cite_note-LiBio14-19\" rel=\"external_link\">[19]<\/a><\/sup>, and Pegasus.<sup id=\"rdp-ebb-cite_ref-DeelmanPeg15_20-0\" class=\"reference\"><a href=\"#cite_note-DeelmanPeg15-20\" rel=\"external_link\">[20]<\/a><\/sup> Our team evaluated each of these systems for their ability to overcome the challenges described above. We found that existing solutions could address some, but not all, of the roadblocks and barriers that were hindering progress on the NCGENES project and that a new solution was needed. While all of the existing workflow systems and pipelines have proven to be effective, each has limitations.<sup id=\"rdp-ebb-cite_ref-BrombergBuild13_21-0\" class=\"reference\"><a href=\"#cite_note-BrombergBuild13-21\" rel=\"external_link\">[21]<\/a><\/sup> MaPSeq is not unique in this regard, but it is responsive to the key features of a decentralized research organization. Specifically, as an SOA, MaPSeq allows for integration with multiple clients and distributed systems, whether local, open source, or commercial, and provides tailored, reusable, automated service solutions that address the varying and evolving needs and preferences of decentralized decision-makers. MaPSeq is scalable and can support both small- and large-scale projects and thus is responsive to the computational needs of all investigators. MaPSeq is efficient and allows for seamless, opportunistic use of distributed compute resources. Finally, the service-oriented, automated approach requires little coordination or communication among individual user groups and thus avoids local nuances in politics and culture. \n<\/p>\n<h2><span class=\"mw-headline\" id=\"MaPSeq_technical_architecture_and_capabilities\">MaPSeq technical architecture and capabilities<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Overview_of_MaPSeq_architecture\">Overview of MaPSeq architecture<\/span><\/h3>\n<p>MaPSeq was designed as an open source, plugin-based SOA solution<sup id=\"rdp-ebb-cite_ref-SprottUnder04_22-0\" class=\"reference\"><a href=\"#cite_note-SprottUnder04-22\" rel=\"external_link\">[22]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-CIOSOA07_23-0\" class=\"reference\"><a href=\"#cite_note-CIOSOA07-23\" rel=\"external_link\">[23]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-BaileyPrin08_24-0\" class=\"reference\"><a href=\"#cite_note-BaileyPrin08-24\" rel=\"external_link\">[24]<\/a><\/sup> that provides modifiable services to make opportunistic use of multiple institutional and cloud-based compute resources in order to efficiently complete the multitude of steps involved in the analysis of large-scale, genomic sequencing data (see Figure 1). The plugin framework of MaPSeq is based on the Open Services Gateway initiative (OSGi). This framework was chosen because of its modular agile architecture and the ability to remotely manage workflow pipelines in an on-demand manner and within a sandboxed environment. Moreover, the investigative team had relevant prior experience with the Open Science Grid Engagement Program, which aims to facilitate collaborative research through advanced distributed computing technologies.\n<\/p><p>MaPSeq and, its sister technology, the Grid Access Triage Engine (GATE), are built on top of ApacheTM Karaf, which is an OSGi-based lightweight container for application deployment. MapSeq works together with GATE to provide extensible capabilities for the analysis of genomic sequencing data, including: pipeline execution and management; meta-scheduling of workflow jobs; opportunistic compute-node utilization and management; secure messaging and data transfer; and client access via web services.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_ReillyInformatics2015_2-3.png\" class=\"image wiki-link\" target=\"_blank\" data-key=\"5fc897bc433610251702c46c0f952637\"><img alt=\"Fig1 ReillyInformatics2015 2-3.png\" src=\"https:\/\/www.limswiki.org\/images\/0\/06\/Fig1_ReillyInformatics2015_2-3.png\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 1.<\/b> An overview of the MaPSeq architecture<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h3><span class=\"mw-headline\" id=\"MaPSeq_pipelines\">MaPSeq pipelines<\/span><\/h3>\n<p>MaPSeq pipelines (Figure 1) are OSGi-based plugins comprised of a number of bundles and\/or services. At a minimum, a MaPSeq pipeline consists of: (1) a Java Message Service destination that exposes a mechanism whereby a user can trigger a pipeline; (2) a workflow designed as a Directed Acyclic Graph (DAG) and consisting of a collection of programmatic tasks; (3) an executor that dequeues the workflows at a customizable frequency (e.g., two workflows every five minutes, ten workflows every three minutes, etc.); and (4) a metadata file that describes all of the aforementioned features and tracks their status. Complex pipelines can be broken into numerous smaller sub-pipelines to enable symbolic check-pointing or fault tolerance. For example, a genomic analysis pipeline can be logically split into two sub-pipelines: an alignment sub-pipeline and a variant calling sub-pipeline. This approach enables a researcher to, for example, modify a step in the variant calling sub-pipeline and re-run that sub-pipeline without the need to re-run the alignment sub-pipeline, thereby reducing the runtime burden. Additionally, this approach allows the sub-pipelines to be reused in other pipelines, thus fostering software re-usability. Of note, all pipelines are project-specific and defined by the needs of the project and research team such that pipeline development is tailored to a specific application.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"HTCondor\">HTCondor<\/span><\/h3>\n<p>HTCondor (Figure 1) serves as a central manager and provides meta-scheduling for MaPSeq via the DAG Manager (DAGMan). MaPSeq workflows are comprised of numerous modules that form the vertices of a DAG. The DAGs can be exported for submission to HTCondor using DAGMan. MaPSeq provides a suite of modules that wrap third-party libraries (e.g., GATK, Picard, etc.) for execution on the grid and that include a number of lifecycle events. These lifecycle events check for valid inputs and outputs, successful execution, and provenance of job metadata, thus ensuring consistency and rapid detection of errors. HTCondor manages serial execution of MaPSeq modules, as well as job-to-machine resource negotiation or \u201cmatchmaking\u201d. The matchmaking process identifies job requirements (e.g., four cores and 4 GB memory required), as defined by the job metadata, and pairs those requirements with available machine attributes (e.g., eight cores and 32 GB memory available). After a MaPSeq module is executed, that module, or job wrapper, persists the job metadata over web services into a <a href=\"https:\/\/www.limswiki.org\/index.php\/PostgreSQL\" title=\"PostgreSQL\" target=\"_blank\" class=\"wiki-link\" data-key=\"a5dd945cdcb63e2d8f7a5edb3a896d82\">PostgreSQL<\/a> database. HTCondor Glideins are used to provision compute resources for the execution of jobs, as described below.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"GATE\">GATE<\/span><\/h3>\n<p>GATE (Figure 1) is a homegrown OSGi-based system that serves as a sister technology for MaPSeq. Whereas MaPSeq uses plugins to execute workflow pipelines, GATE uses plugins to access compute resources. GATE continuously monitors a local HTCondor instance for idle jobs and profiles compute resources for availability. If an idle job is detected, then GATE uses plugins to submit an HTCondor Glidein to the most appropriate compute resource, which then joins the local HTCondor pool. GATE defers matchmaking to the HTCondor Negotiator, which uses daemons to perform the matchmaking. GATE grows and shrinks the number of Glideins by assessing the number of running and idle local jobs against the number of running and idle Glidein jobs on the compute resource grid. After a Glidein is activated, it registers back to the HTCondor Central Manager as an available resource. This approach enables jobs to be both site-specific and site-agnostic.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Security.2C_interfaces.2C_and_administration\">Security, interfaces, and administration<\/span><\/h3>\n<p>Of significance, both MaPSeq and GATE use Secure SHell (SSH) technology, running with daemons, for authentication and data transfer. This level of security is particularly important for applications such as genomics that involve the movement of sensitive patient data.\n<\/p><p>Clients can interface with MaPSeq using Apache\u2122 CXF (Figure 1), which is an industry-standard web service. Both Simple Object Access Protocol (SOAP) and Representational State Transfer (RESTful) services are supported by Apache CXF. Pipeline invocations are triggered via a JavaScript Object Notation (JSON)-formatted message to an ApacheTM ActiveMQ destination. The JSON message contains the mapping between a MaPSeq-managed sample file instance and a workflow run instance. A pipeline-specific \u201cmessage listener\u201d then determines if the message is legitimate for subsequent processing. For genomic sequencing data, this process may involve verification that an object layer in the data file specifies that the data file contains raw sequencing data and sufficient metadata. A rich set of MaPSeq reports can be generated and sent to a client via email, for review and detection of potential problems (see example in Figure 2).\n<\/p><p>Apache Karaf is unique among containers in that it embeds an SSH daemon to enable a client to administratively manage pipeline deployment within a sandboxed environment. MaPSeq pipelines can be added, removed, or altered without having to stop the container, thereby provisioning a continuous, uninterrupted environment to execute new pipelines while existing pipelines are running. This accessibility allows for a pipeline developer to independently iterate on pipeline improvements.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_ReillyInformatics2015_2-3.png\" class=\"image wiki-link\" target=\"_blank\" data-key=\"7c28dd492e269825610baf1ae98a4f2c\"><img alt=\"Fig2 ReillyInformatics2015 2-3.png\" src=\"https:\/\/www.limswiki.org\/images\/5\/58\/Fig2_ReillyInformatics2015_2-3.png\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 2.<\/b> An example of a MaPSeq output log showing the duration of a job (total and average minutes (min) over a one-week time period) by specific task<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<h2><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h2>\n<p>Genomics research within an academic environment presents numerous challenges. In addition to the computational and technical challenges inherent in genomics research<sup id=\"rdp-ebb-cite_ref-KoboldtChal10_1-1\" class=\"reference\"><a href=\"#cite_note-KoboldtChal10-1\" rel=\"external_link\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-KahnOn11_2-1\" class=\"reference\"><a href=\"#cite_note-KahnOn11-2\" rel=\"external_link\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-GreenClin14_3-1\" class=\"reference\"><a href=\"#cite_note-GreenClin14-3\" rel=\"external_link\">[3]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-DeweyClin14_4-2\" class=\"reference\"><a href=\"#cite_note-DeweyClin14-4\" rel=\"external_link\">[4]<\/a><\/sup>, there are complex sociological, psychological, cultural, and political challenges that affect operations within academic institutions and indeed many other types of organizations.<sup id=\"rdp-ebb-cite_ref-WilliamsTheSoc96_25-0\" class=\"reference\"><a href=\"#cite_note-WilliamsTheSoc96-25\" rel=\"external_link\">[25]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-LorenziAnt97_26-0\" class=\"reference\"><a href=\"#cite_note-LorenziAnt97-26\" rel=\"external_link\">[26]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-JaspersonSoc99_27-0\" class=\"reference\"><a href=\"#cite_note-JaspersonSoc99-27\" rel=\"external_link\">[27]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-SassenTow02_28-0\" class=\"reference\"><a href=\"#cite_note-SassenTow02-28\" rel=\"external_link\">[28]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-SchmidtInt05_29-0\" class=\"reference\"><a href=\"#cite_note-SchmidtInt05-29\" rel=\"external_link\">[29]<\/a><\/sup> Moreover, academic biomedical research institutions tend to be decentralized in their organizational structure. Whereas centralized organizations tend to function within a simple organizational design, with singular decision-making, top-level operational control, a consolidated budget, strong\/clear communication channels, uniform culture and politics, and a high degree of operational efficiency, decentralized organizations, in contrast, operate within a complex organizational design, with distributed decision-making, localized operations and budgets, weak communication channels, nuances in culture and politics across academic units, and minimal operational efficiency.<sup id=\"rdp-ebb-cite_ref-OrlikowskiTech01_5-1\" class=\"reference\"><a href=\"#cite_note-OrlikowskiTech01-5\" rel=\"external_link\">[5]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-HeidenCent07_6-1\" class=\"reference\"><a href=\"#cite_note-HeidenCent07-6\" rel=\"external_link\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-JainToCent13_7-1\" class=\"reference\"><a href=\"#cite_note-JainToCent13-7\" rel=\"external_link\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-IngramCent15_8-1\" class=\"reference\"><a href=\"#cite_note-IngramCent15-8\" rel=\"external_link\">[8]<\/a><\/sup>\n<\/p><p>MaPSeq provides a reusable, service-oriented solution that addresses the diverse and evolving computational needs of decentralized decision-makers and scales to support both small- and large-scale projects. The automated approach requires little coordination or communication among individual user groups and thus avoids human roadblocks that may otherwise decrease efficiency. By leveraging the OSGi framework and Apache Karaf, MaPSeq allows for quick development iterations on MaPSeq pipeline plugins; pipelines can be created, altered, deployed, triggered, and removed without having to stop and restart the container. Finally, the use of HTCondor as a meta-scheduler and the addition of GATE as a sister technology allow MaPSeq to extend compute cluster capacity and make opportunistic use of distributed compute resources across the university campus.\n<\/p><p>In an environment of legacy systems, distributed and uncoordinated decision-making and compute resources, diverse and evolving user needs, and political and cultural resistance to change, centralized technical solutions will not promote efficient and effective biomedical research. SOA solutions provide the flexibility, scalability, extensibility, accessibility, interoperability, generalizability, achievability, and functionality required to attain efficient and effective, transformative biomedical research within a decentralized organization.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Limitations\">Limitations<\/span><\/h3>\n<p>Like any scientific workflow pipeline, MaPSeq is not without limitations.<sup id=\"rdp-ebb-cite_ref-BrombergBuild13_21-1\" class=\"reference\"><a href=\"#cite_note-BrombergBuild13-21\" rel=\"external_link\">[21]<\/a><\/sup> First, while the underlying technology is open source and freely available, there is a considerable learning curve involved in implementation of the technology. Second, GATE is a homegrown solution and requires institution-specific adaptation before it can be adopted for use. Third, the MaPSeq solution must be continuously assessed against the evolving needs of relevant stakeholders, including users, patients, investigators, institutional administrators, and policy makers.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>SOA solutions such as MaPSeq are well suited to overcome the many challenges to biomedical research that are inherent in a decentralized academic institution. MaPSeq has transformed genomics research at our institution and currently supports several large genomics research projects, as well as a few small ones. While MaPSeq was originally termed as an acronym for \u201cMassively Parallel Sequencing\u201d and designed to support genomics research, we note that the general architecture and approach can be adapted for other complex or computationally-intense workflows.\n<\/p><p>Finally, we note that MaPSeq (version 5.0) is available through a University of North Carolina Open Source Public License (version 1.1, \u00a92004). The only prerequisites are Java 1.7+, Apache\u2122 Maven 3, and a network connection (full technical specifications and installation\/operational instructions can be found at<sup id=\"rdp-ebb-cite_ref-RENCIMaP15_30-0\" class=\"reference\"><a href=\"#cite_note-RENCIMaP15-30\" rel=\"external_link\">[30]<\/a><\/sup>, with an accompanying RENCI technical report at reference<sup id=\"rdp-ebb-cite_ref-RENCITR14_31-0\" class=\"reference\"><a href=\"#cite_note-RENCITR14-31\" rel=\"external_link\">[31]<\/a><\/sup>).\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>This project was conceptualized and implemented by RENCI and the UNC High-Throughput Sequencing Facility, in collaboration with Information Technology Services Research Computing and the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill and with funding from the National Institutes of Health (1R01-DA030976-01, 1U01-HG006487-01, 5UL1-RR025747-03, 1U19-HD077632-01, and 1U01-HG007437-01). The authors acknowledge the contributions of Corbin Jones, Associate Professor in the Department of Biology, and Jeff Roach, Senior Scientific Research Associate for Research Computing, Information Technology Services, University of North Carolina at Chapel Hill, to the design and implementation of MaPSeq. Karamarie Fecho, provided writing support for this manuscript, and RENCI provided funding for that support.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Author_contributions\">Author contributions<\/span><\/h2>\n<p>Jason Reilly designed and implemented MaPSeq with assistance from Phillips Owen as a replacement of earlier work by Charles Schmitt and based on prior work by John McGee, Kirk Wilhelmsen oversaw the implementation of MapSeq. Stanley Ahalt provided general guidance and facilities support for the development and implementation of MaPSeq.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conflicts_of_interest\">Conflicts of interest<\/span><\/h2>\n<p>The authors declare no conflict of interest.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<ol class=\"references\">\n<li id=\"cite_note-KoboldtChal10-1\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-KoboldtChal10_1-0\" rel=\"external_link\">1.0<\/a><\/sup> <sup><a href=\"#cite_ref-KoboldtChal10_1-1\" rel=\"external_link\">1.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Koboldt, D.C.; Ding, L.; Mardis, E.R.; Wilson, R.K. 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(2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2881353\" target=\"_blank\">\"Ergatis: A web interface and scalable software system for bioinformatics workflows\"<\/a>. <i>Bioinformatics<\/i> <b>26<\/b> (12): 1488-1492. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fbioinformatics%2Fbtq167\" target=\"_blank\">10.1093\/bioinformatics\/btq167<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2881353\/\" target=\"_blank\">PMC2881353<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20413634\" target=\"_blank\">20413634<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2881353\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2881353<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Ergatis%3A+A+web+interface+and+scalable+software+system+for+bioinformatics+workflows&rft.jtitle=Bioinformatics&rft.aulast=Orvis%2C+J.%3B+Crabtree%2C+J.%3B+Galens%2C+K.+et+al.&rft.au=Orvis%2C+J.%3B+Crabtree%2C+J.%3B+Galens%2C+K.+et+al.&rft.date=2010&rft.volume=26&rft.issue=12&rft.pages=1488-1492&rft_id=info:doi\/10.1093%2Fbioinformatics%2Fbtq167&rft_id=info:pmc\/PMC2881353&rft_id=info:pmid\/20413634&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2881353&rfr_id=info:sid\/en.wikipedia.org:Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-KohaneATrans11-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-KohaneATrans11_11-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kohane, I.S.; Churchill, S.E.; Murphy, S.N. (2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3277623\" target=\"_blank\">\"A translational engine at the national scale: Informatics for integrating biology and the bedside\"<\/a>. <i>Journal of the American Medical Informatics Association<\/i> <b>19<\/b> (2): 181-185. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1136%2Famiajnl-2011-000492\" target=\"_blank\">10.1136\/amiajnl-2011-000492<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3277623\/\" target=\"_blank\">PMC3277623<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22081225\" target=\"_blank\">22081225<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3277623\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3277623<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+translational+engine+at+the+national+scale%3A+Informatics+for+integrating+biology+and+the+bedside&rft.jtitle=Journal+of+the+American+Medical+Informatics+Association&rft.aulast=Kohane%2C+I.S.%3B+Churchill%2C+S.E.%3B+Murphy%2C+S.N.&rft.au=Kohane%2C+I.S.%3B+Churchill%2C+S.E.%3B+Murphy%2C+S.N.&rft.date=2011&rft.volume=19&rft.issue=2&rft.pages=181-185&rft_id=info:doi\/10.1136%2Famiajnl-2011-000492&rft_id=info:pmc\/PMC3277623&rft_id=info:pmid\/22081225&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC3277623&rfr_id=info:sid\/en.wikipedia.org:Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-DinovApp11-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-DinovApp11_12-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Dinov, I.D.; Torri, F.; Macciardi, F. et al. 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Retrieved 16 April 2015<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Principles+of+Service+Oriented+Architecture&rft.atitle=SlidePlayer&rft.aulast=Bailey%2C+M.&rft.au=Bailey%2C+M.&rft.date=2008&rft.pub=SlidePlayer.com%2C+Inc&rft_id=http%3A%2F%2Fslideplayer.com%2Fslide%2F701834%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-WilliamsTheSoc96-25\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-WilliamsTheSoc96_25-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Williams, R.; Edge, D. (1996). \"The social shaping of technology\". <i>Research Policy<\/i> <b>25<\/b> (6): 865\u2013899. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2F0048-7333%2896%2900885-2\" target=\"_blank\">10.1016\/0048-7333(96)00885-2<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+social+shaping+of+technology&rft.jtitle=Research+Policy&rft.aulast=Williams%2C+R.%3B+Edge%2C+D.&rft.au=Williams%2C+R.%3B+Edge%2C+D.&rft.date=1996&rft.volume=25&rft.issue=6&rft.pages=865%E2%80%93899&rft_id=info:doi\/10.1016%2F0048-7333%2896%2900885-2&rfr_id=info:sid\/en.wikipedia.org:Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LorenziAnt97-26\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-LorenziAnt97_26-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Lorenzi, N.M.; Riley, R.T.; Blyth, A.J.C. et al. (1997). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC61497\" target=\"_blank\">\"Antecedents of the people and organizational aspects of medical informatics: Review of the literature\"<\/a>. <i>Journal of the American Medical Informatics Association<\/i> <b>4<\/b> (62): 79-93. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1136%2Fjamia.1997.0040079\" target=\"_blank\">10.1136\/jamia.1997.0040079<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC61497\/\" target=\"_blank\">PMC61497<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/9067874\" target=\"_blank\">9067874<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC61497\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC61497<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Antecedents+of+the+people+and+organizational+aspects+of+medical+informatics%3A+Review+of+the+literature&rft.jtitle=Journal+of+the+American+Medical+Informatics+Association&rft.aulast=Lorenzi%2C+N.M.%3B+Riley%2C+R.T.%3B+Blyth%2C+A.J.C.+et+al.&rft.au=Lorenzi%2C+N.M.%3B+Riley%2C+R.T.%3B+Blyth%2C+A.J.C.+et+al.&rft.date=1997&rft.volume=4&rft.issue=62&rft.pages=79-93&rft_id=info:doi\/10.1136%2Fjamia.1997.0040079&rft_id=info:pmc\/PMC61497&rft_id=info:pmid\/9067874&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC61497&rfr_id=info:sid\/en.wikipedia.org:Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-JaspersonSoc99-27\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-JaspersonSoc99_27-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Jasperson, J.S.; Sambamurthy, V.; Zmud, R.W. 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(2002). \"Towards a sociology of information technology\". <i>Current Sociology<\/i> <b>50<\/b> (3): 365-388. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1177%2F0011392102050003005\" target=\"_blank\">10.1177\/0011392102050003005<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Towards+a+sociology+of+information+technology&rft.jtitle=Current+Sociology&rft.aulast=Sassen%2C+S.&rft.au=Sassen%2C+S.&rft.date=2002&rft.volume=50&rft.issue=3&rft.pages=365-388&rft_id=info:doi\/10.1177%2F0011392102050003005&rfr_id=info:sid\/en.wikipedia.org:Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-SchmidtInt05-29\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-SchmidtInt05_29-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Schmidt, J.; Lyle, D. (2005). <i>Integration Competency Center: An Implementation Methodology<\/i>. Redwood City, CA: Informatics Corp. pp. 153. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" target=\"_blank\">ISBN<\/a> 9780976916307.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Integration+Competency+Center%3A+An+Implementation+Methodology&rft.aulast=Schmidt%2C+J.%3B+Lyle%2C+D.&rft.au=Schmidt%2C+J.%3B+Lyle%2C+D.&rft.date=2005&rft.pages=pp.%26nbsp%3B153&rft.place=Redwood+City%2C+CA&rft.pub=Informatics+Corp&rft.isbn=9780976916307&rfr_id=info:sid\/en.wikipedia.org:Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-RENCIMaP15-30\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-RENCIMaP15_30-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/jdr0887.github.io\/MaPSeq-API\/index.html\" target=\"_blank\">\"Massively Parallel Sequencing\"<\/a>. University of North Carolina at Chapel Hill. 2015<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/jdr0887.github.io\/MaPSeq-API\/index.html\" target=\"_blank\">http:\/\/jdr0887.github.io\/MaPSeq-API\/index.html<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 13 July 2015<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Massively+Parallel+Sequencing&rft.atitle=&rft.date=2015&rft.pub=University+of+North+Carolina+at+Chapel+Hill&rft_id=http%3A%2F%2Fjdr0887.github.io%2FMaPSeq-API%2Findex.html&rfr_id=info:sid\/en.wikipedia.org:Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-RENCITR14-31\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-RENCITR14_31-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/renci.org\/technical-reports\/mapseq-computational-and-analytical-workflow-manager\/\" target=\"_blank\">\"TR-14-03 MaPSeq, A Computational and Analytical Workflow Manager for Downstream Genomic Sequencing\"<\/a>. RENCI. 03 June 2014<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/renci.org\/technical-reports\/mapseq-computational-and-analytical-workflow-manager\/\" target=\"_blank\">http:\/\/renci.org\/technical-reports\/mapseq-computational-and-analytical-workflow-manager\/<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 13 July 2015<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=TR-14-03+MaPSeq%2C+A+Computational+and+Analytical+Workflow+Manager+for+Downstream+Genomic+Sequencing&rft.atitle=&rft.date=03+June+2014&rft.pub=RENCI&rft_id=http%3A%2F%2Frenci.org%2Ftechnical-reports%2Fmapseq-computational-and-analytical-workflow-manager%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192203\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.759 seconds\nReal time usage: 0.788 seconds\nPreprocessor visited node count: 25059\/1000000\nPreprocessor generated node count: 37586\/1000000\nPost\u2010expand include size: 214308\/2097152 bytes\nTemplate argument size: 69378\/2097152 bytes\nHighest expansion depth: 18\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 755.785 1 - -total\n 86.55% 654.155 1 - Template:Reflist\n 75.72% 572.283 31 - Template:Citation\/core\n 56.80% 429.311 20 - Template:Cite_journal\n 18.11% 136.875 9 - Template:Cite_web\n 9.08% 68.629 51 - Template:Citation\/identifier\n 8.41% 63.590 1 - Template:Infobox_journal_article\n 8.06% 60.902 1 - Template:Infobox\n 5.32% 40.207 2 - Template:Cite_book\n 4.91% 37.074 38 - Template:Citation\/make_link\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:8232-0!*!0!!en!5!* and timestamp 20181214192202 and revision id 24421\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution\">https:\/\/www.limswiki.org\/index.php\/Journal:MaPSeq,_a_service-oriented_architecture_for_genomics_research_within_an_academic_biomedical_research_institution<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","2dc8d868e85040728288505b6c391110_images":["https:\/\/www.limswiki.org\/images\/0\/06\/Fig1_ReillyInformatics2015_2-3.png","https:\/\/www.limswiki.org\/images\/5\/58\/Fig2_ReillyInformatics2015_2-3.png"],"2dc8d868e85040728288505b6c391110_timestamp":1544815322,"8552328b588cc33465f115d2b29dced0_type":"article","8552328b588cc33465f115d2b29dced0_title":"Djeen (Database for Joomla!\u2019s Extensible Engine): A research information management system for flexible multi-technology project administration (Stahl et al. 2013)","8552328b588cc33465f115d2b29dced0_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Djeen_(Database_for_Joomla!%E2%80%99s_Extensible_Engine):_A_research_information_management_system_for_flexible_multi-technology_project_administration","8552328b588cc33465f115d2b29dced0_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:Djeen (Database for Joomla!\u2019s Extensible Engine): A research information management system for flexible multi-technology project administration\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nDjeen (Database for Joomla!\u2019s Extensible Engine): A research information management system for flexible multi-technology project administrationJournal\n \nBMC Research NotesAuthor(s)\n \nStahl, Olivier; Duvergey, Hugo; Guille, Arnaud; Blondin, Fanny; Del Vecchio, Alexandre; Finetti, Pascal; Granjeaud, Samuel; Vigy, Oana; Bidaut, GhislainAuthor affiliation(s)\n \nUniversit\u00e9s de Montpellier, Institut de G\u00e9nomique Fonctionnelle, INSERMPrimary contact\n \nEmail: ghislain.bidaut@inserm.frYear published\n \n2013Volume and issue\n \n6Page(s)\n \n223DOI\n \n10.1186\/1756-0500-6-223ISSN\n \n1756-0500Distribution license\n \nCreative Commons Attribution 2.0 GenericWebsite\n \nhttp:\/\/bmcresnotes.biomedcentral.com\/articles\/10.1186\/1756-0500-6-223Download\n \nhttp:\/\/bmcresnotes.biomedcentral.com\/track\/pdf\/10.1186\/1756-0500-6-223 (PDF)\n\nContents\n\n1 Abstract \n2 Findings \n\n2.1 Background \n2.2 Related work \n2.3 Implementation \n2.4 Content management system \n\n2.4.1 Integration within the Joomla! CMS \n2.4.2 Data organization and Djeen elements \n2.4.3 Web interface and Djeen functionality \n\n\n\n\n3 Results and discussion \n\n3.1 Preparing the project hierarchy within Djeen \n3.2 Importing microarray data (CELs files) \n3.3 Adding and formatting a MIAME-compliant transcriptome template \n\n\n4 Conclusion \n5 Availability and requirements \n6 Abbreviations \n7 Declarations \n\n7.1 Acknowledgements \n7.2 Funding \n7.3 Competing interests \n7.4 Authors\u2019 contributions \n\n\n8 References \n9 Notes \n\n\n\nAbstract \nBackground: With the advance of post-genomic technologies, the need for tools to manage large scale data in biology becomes more pressing. This involves annotating and storing data securely, as well as granting permissions flexibly with several technologies (all array types, flow cytometry, proteomics) for collaborative work and data sharing. This task is not easily achieved with most systems available today.\nFindings: We developed Djeen (Database for Joomla!\u2019s Extensible Engine), a new Research Information Management System (RIMS) for collaborative projects. Djeen is a user-friendly application, designed to streamline data storage and annotation collaboratively. Its database model, kept simple, is compliant with most technologies and allows storing and managing of heterogeneous data with the same system. Advanced permissions are managed through different roles. Templates allow Minimum Information (MI) compliance.\nConclusion: Djeen allows managing project associated with heterogeneous data types while enforcing annotation integrity and minimum information. Projects are managed within a hierarchy and user permissions are finely-grained for each project, user and group.\nDjeen Component source code (version 1.5.1) and installation documentation are available under CeCILL license from http:\/\/sourceforge.net\/projects\/djeen\/files and supplementary material.\nKeywords: Database, CMS, Minimum Information, RIMS\n\nFindings \nBackground \nAdvent of post-genomic era has seen a massive adoption of technologies that fundamentally changed the way biological assays are designed, data generated and collected, and further analyzed. Typical biological\/genomic projects are now involving geographically spread laboratories that conduct large scale experiments that need to be analyzed in an integrated way.[1] Data must therefore be thoroughly annotated and mutually shared with fine-grained user permissions. It is also crucial that data annotation meet Minimum Information (MI) as well as standards defined in the lab where these data were generated. MI standards have been initially defined for microarray experiments (MIAME)[2] and have since been extended to other technologies, including flow cytometry (MIFlowCyt)[3] and proteomics (MIAPE).[4]\nSeveral Laboratory Information Management Systems (LIMS) have been created over the years. Even though these have proven usefulness in instruments everyday usage, increasing data integration needs have underlined typical LIMS drawbacks in most laboratories.\nFirstly, LIMS are usually conceived to manage data issued from a single technology type, such as DNA microarray[5][6], proteomics[7], high throughput sequencing.[8] This complicates further data integration and analysis since separate data types are typically stored on separate LIMS.\nSecondly, any data evolution or reorganization implies re-engineering and adopting a new LIMS. Most LIMS rather meet lab requirements at a given instant without taking into account the fact that technology, data formats, structures and devices are constantly changing and evolving, which restrains long-term use of the system.\nFinally, each additional device installed in the laboratory implies training users on new laboratory practices since all LIMS are designed with different user interfaces (UIs). Subsequent fragmentation of systems and resources has a negative impact on quality control (QC). Moreover, administrating heterogeneous LIMS is a complex task that cannot be assumed by a typical wet laboratory structure that does not have the bioinformatics expertise and development resources to adapt tools to its specific needs. Because of these limits, typical LIMS do not favor interdisciplinary and translational collaborations and thus prevent the transfer of knowledge among laboratories generating heterogeneous information that has to be integrated.\nIn this report, we describe the Database for Joomla!\u2019s Extensible Engine (Djeen), a new generation of LIMS that features a simple technological conception coupled with an advanced capacity of adaptation to be directly used or easily adapted to different technologies. The Djeen database scheme is kept simple to maximize generalization and application possibilities. Only data organization and metadata (annotations) are stored within a database, while experimental data is organized in the file system. In addition, the program is adaptable to any technology since no technology-dependent semantics were used in the code. Djeen can therefore evolve with user and laboratory needs. Since most technology can be managed with Djeen, this allows for unification of all information systems within the lab.\nDjeen features a large functionality set (import\u2013export, multi-technological implementation, advanced user\/groups permissions) and is conceptually more advanced than other LIMS publicly available. Djeen qualifies as a Research Information Management System.[9] As such, Djeen addresses four fundamental issues in high throughput biomedical data management: data organization, data sharing, collaboration and publication.\nData organization consists in allowing straightforward data retrieval without the presence of the person who generated them. Therefore, data must be securely stored in a standardized way.\nData sharing consists in allowing several collaborators to access the same data, while avoiding data duplication or data reformatting. Collaboration is an important aspect of dataset entry and development; it allows several collaborators to manage and maintain the same data, which means that the data is not organized by a single individual. Finally, data publication encompasses secure data sharing for a large group of users (over the Internet or intranet).\n\nRelated work \nMany LIMS have been developed by large companies to respond to precise specifications responding to needs by a given laboratories. There exists also generic commercial LIMS that can be customized to specific needs. Some of them were confronted to a real situation in a large cell production facility.[10] In this paper, all facility members compared several LIMS according to multiple criteria and adopted a commercial LIMS. A consultant was hired for one year to adapt the LIMS to their specific needs, and adapt other modules, which implies significant means. On the contrary, Djeen was conceived to be used by small research groups with no or little dedicated bioinformatics support and few resources.\nA commercial LIMS is hence not a \u2018ready to use\u2019 program and necessitate a very complex installation specific to end-user usage. Also, there is a strong dependence on the software\u2019s vendor and his ability to follow up on the product and insure longevity, which is not guaranteed. Djeen being open source and under CeCILL license, anyone can contribute to it and it will stay available.\nA number of publicly available open source LIMS exist, and partially addressed the issues described in this paper. Many LIMS are inherently limited to a single technology type, i.e. Proteomics (ms_lims[7]) or microarray (BASE[6], or the Longhorn Array Database[5]), which is a serious limitation for many laboratories, who need the same system to store all their data. Djeen allows for managing heterogeneous datasets within the same system.\nOther LIMS can be used to manage multiple technologies. MADMAX[11] allows for the storage and analysis of heterogeneous genomics data in the same repository. However, its implementation is rather complex and based on an Oracle (Redwood City, CA, USA) Database Management System (DBMS), which can be a limiting factor for some laboratories with limited resources. Djeen is based solely on open-source technology, being its database (MySQL or PostgreSQL) or the Content Management System (Joomla!). SIGLa (Systema Integrado de Ger\u00eancia de Laboratori\u00f3s[12]) is based on a workflow management tool that makes it also adaptable to multiple usages. The concept of workflows is not needed by all users and increases dramatically the complexity of data entry. Therefore, workflows are not hard-coded into Djeen to avoid technology-specific code but can be used with annotations when needed.\nBonsaiLIMS[13] is a lightweight LIMS developed initially to centralize patient records for translational research. However, BonsaiLIMS features only a very limited model and functionality set as compared to Djeen, which works \u201cout of the box\u201d after a deployment from the Joomla!\u2019s component deployment interface. Djeen features more functionality, such as templates group permission management and data export.\n\nImplementation \nDjeen is a Research Information Management System developed to meet the four type of functionalities described above:\nData organization\nDjeen structures data into a hierarchical system allowing creating and managing complex data structures hierarchically with high flexibility while enforcing standardization and Minimum information standards. Djeen is able to manage projects containing heterogeneous data types while maintaining homogeneous annotations through the optional use of templates.\nData sharing\nData is shared through fine-grained user permissions to strengthen data security. Several user roles are defined and granted with gradually increasing permissions. This allows managing data that is completely confidential as well as sharing it with specified users and groups, or release it publicly over the Internet.\nUser collaboration\nUser collaboration goes beyond data sharing. It implies that datasets are built and contributed to by several collaborators while general project structure and annotations are under the control of a project owner. In Djeen, once permissions are set to appropriate users or groups, project administrators can control homogeneity of annotations with templates. Templates allow enforcing data integrity and homogeneity as well as quality control (QC). Their role is detailed in the \u2018Data organization and Djeen elements\u2019 section.\nPublication\nTo be able to publish datasets and meet needs for data sharing and collaborations, Djeen was developed as a Web application.\nDjeen software administration\nA fifth item was taken into account when designing Djeen. Djeen was conceived as a Web application that is simple to install, easy to learn and to administrate. A Djeen instance is maintainable by a research group with no or little dedicated bioinformatics human resources, and usable with a minimal training.\n\nContent management system \nDjeen was developed as an extension of the Joomla! Content Management System (CMS).\nCMS are a category of applications allowing the management and the publication of content, \u201ccontent\u201d being defined rather loosely (see Mooney and Baenziger[14] for a review of CMS usage in bioinformatics). In our case, it is related to scientific information, and more precisely, data and their annotations. CMS are very attractive since they are characterized by a modular design and allow for development of new applications for visualizing content. Reuse of CMS tools for web application development potentially simplifies things and allows programmers to focus on the application features instead of spending time on redeveloping a number of generic functionalities, such as site administration and visual design.\nAs compared to a home grown development, developing a web application as a CMS extension allowed us to maximize the security by taking advantage of the existing authentication system. Additionally, security does not depend entirely on the application itself but also on the local network configuration.\nThe appropriate choice for a CMS is crucial especially considering security issues.[14] We carefully choose the CMS on several criteria, including active support, presence of a documented API, quality of the interface in terms of look and feel, and simplicity of administration and installation. In regard to all these considerations, we decided to develop Djeen as a Joomla! 1.5 component.\nJoomla! version 1.5 is an open-source Content Management System (http:\/\/www.joomla.org) featuring a documented API to create advanced extensions based on a Model-View-Controller (MVC) Design Pattern.[15] Additionally, it is backed-up by a large community of developers that quickly releases security patches and new versions and update documentation.\n\nIntegration within the Joomla! CMS \nTo understand how Djeen interacts with Joomla!, a summary of its architecture and function is given. As shown in Figure 1, Joomla! was conceived as a three tier system based on this MVC structure, to separate data access (Models), rendering system (Views) and actions (Controllers).\n\n\n\n\n\n\n\n\n\n Figure 1. Joomla! API and Djeen implementation. This figure shows the Joomla's API and the mechanisms of interaction between Djeen and Joomla!. The right part of the figure represents the three tiered Joomla! API (adapted from Joomla's documentation, (http:\/\/docs.joomla.org\/\u200bFramework\/\u200b1.\u200b5#Packages_\u200band_\u200bClasses). This architecture defines the software from data access to the final application display through a Model-View-Controller (MVC) model. The left part of the figure shows specific Djeen main components (Djeen database, file repository) as well as Joomla!'s components (Joomla!'s database, containing user information and component configuration) reused by Djeen. Djeen uses the framework layer to interact with Joomla! and manages users\u2019 connections and the application layer for display.\n\n\n\nThe purpose of the framework layer is to manage data within Joomla!, it includes different classes and libraries to access database and file system. The application layer manages Joomla!'s UI, such as administration panel and public website. Finally, the extension layer includes templates to change the website rendering and extensions to change or extend Joomla!'s functionalities. Modules are used to display additional data bits and pieces into specific \u2018boxes\u2019. Components are a more advanced type of extensions that allow developing full fledged applications while granted access to the Joomla! API. Djeen is a Component and implements its own database and a dedicated repository.\nBy using the Joomla! API, Djeen is deployed and managed from the Joomla! administrator panel. No third party software or client is needed and compatibility was validated on the Mozilla Firefox\u00ae and Google Chrome\u00ae browsers (current versions as of publication). The application is embedded to the Joomla! front-end website through the application layer.\nData security is ensured by a complete separation of Djeen and Joomla! databases to facilitate backup and keeping Djeen as an independent component at every level. Djeen objects are stored within a specific relational database (PostgreSQL and MySQL drivers are provided) while files are simply stored in the file system. The connection to the Djeen external database is ensured by a second security level that uses an encrypted password stored into the component configuration. Several databases can be maintained, and each instance has its own password.\n\nData organization and Djeen elements \nIn this section, Djeen objects (such as Projects and Templates) are refereed to with a capital letter. These are simply referred to as generic terms in subsequent sections.\nFigure 2 shows the Djeen data model main elements and the duality files-database. The File object is the central piece of information within Djeen, since it represents the lowest granularity level in most high-throughput analyses. This model and the associated code were designed to be technology-independent and free of specific semantics to stay adaptable to multiple data types and as generalizable as possible. In the database side, the main Djeen entity to manage data is the Project. Projects are organized in a hierarchy and a Project can reference multiple sub-Projects. This hierarchy is mirrored in the corresponding directory organization on the file system side. Projects are linked to Files issued from experimentation or analysis using this directory organization. Projects are equivalent to folders and files are simply stored within these folders. This organization is very intuitive and simple to manage and backup.\n\n\n\n\n\n\n\n\n\n Figure 2. Djeen data organization model. Djeen separates Projects hierarchy, Templates and Annotations on one side (these are stored in the Djeen relational database) and the data itself (stored in the file system). Data stored into the database are divided into several objects, each of them being represented by a database table, linked to a class model in the MVC architecture. Project is the primary Djeen organizational element. It allows the construction of a hierarchical tree of sub-Projects and includes metadata about itself and stored files. The File object is the most basic and central piece of information within Djeen, since it represents the lowest granularity level in most high-throughput analyses. This project\/files hierarchical tree is structurally mirrored into the file system. Metadata are divided into Characteristics (related to Projects) and Annotations (related to Files). Those two types of metadata can be saved into Templates, allowing users to reuse them into other Projects. The Users object is a specific table containing user and group information. It supersedes the Joomla! system by formation specific to Djeen that allows managing specific permissions and groups while permitting reuse of all the features already implemented in the CMS, such as authentication or e-mailing.\n\n\n\nFiles and Projects are annotated by two types of metadata. The Annotations are related to Files and the Characteristics are specifically related to Projects. Annotations contain sample or condition-specific information while Characteristics contain general Project information and descriptions.\nTo allow reusing metadata for similar Projects, Templates were introduced. They allow storing a predefined list of Annotations and Characteristics that will be used when creating a Project. Templates have specific owners and cannot be modified once they are used in a Project to prevent further unwanted modifications.\nNo constrains are imposed by Djeen implementation on Project structure or Annotations types. This allows for the use of multiple data types in the same management system. However, Projects manager can optionally use Templates to enforce the type of Annotations to be provided by the experimentalist and enforce MI compliance if necessary. Data provenance, for instance, can be encoded as a mandatory annotation field. Templates also allow structuring the Project, to permit further data integration and promote QC by being consistent with MI and sample annotations. In addition to Templates and Annotations, Djeen allows highlighting (with a flag) a specific annotation that corresponds to the biological question asked in a Project.\nDjeen allows data sharing under an advanced permission system that supersedes the native user management system of Joomla! by adding specific information. Four roles have been defined (Superadministrator, Administrator, Moderator, and User) granted with specific permissions on data, User\/Groups and Template management. A given Project is owned by an Administrator or a Moderator who has the role of Project owner. He controls annotations and user permissions on files. Projects and sub-Projects permissions can be granted to specific user groups to finely manage access of large scale collaborative projects.\n\nWeb interface and Djeen functionality \nDjeen\u2019s UI was designed to facilitate navigation and manipulation of data as intuitively as possible and features a fast learning curve. To optimize interoperability with Joomla! and maximize its maintainability, Djeen was mainly developed in PHP. A data uploader was developed in Perl to allow massive data transfers (of several GBs) for importation of large sets of raw data. All table rendering and user interaction code was implemented an Ajax\/Javascript layer through the Mootools library (http:\/\/mootools.net). Additionally, a customizable dialog box was made available for administrators to display information such as an End-User License Agreement (EULA) for users, as well as any other information or error messages.\nThe Djeen UI main elements are represented Figure 3. Main icons (A) allow for quick access to projects and experiments and search dialog. Other icons (B) allow for template management, user and group management, current user options, and connection to the system. The breadcrumbs (C) allow for navigating project hierarchy. Panel (D) shows the main project view. It features general description, owner and creation date, template used and characteristics table (H). The tabs (E) allow for management of sub-projects, files, annotations, project history and specific user permissions. The \u201cFiles\u201d tab opens a panel (overlaid here) displaying the list of files linked to the current project (F), annotated using the annotations table (G). Moreover, users can generate snapshots of the whole project by using the \u201cHistory\u201d function in (E). Such a snapshot allows project manager to generate a data freeze for publication of a project. A notification zone displays messages returned by the system (I) in an elegant and non-intrusive manner. (I) icons are functions present in most tables, namely \u201cPrint\u201d and \u201cExport\u201d. Icons (J) are general project actions including \u201cPrint\u201d, \u201cNew Project\u201d, \u201cEdit\u201d, \u201cCopy as template\u201d, \u201cCopy in Clipboard\u201d and \u201cClear Clipboard\u201d.\n\n\n\n\n\n\n\n\n\n Figure 3. Djeen Web Interface. This figure shows the Djeen web interface opened on the project view, as seen as connected as a user with read permissions. The web interface is embedded within Joomla! (Not represented here), and presents all elements related to this particular view as well as some elements common to several views. Among the common element to all Djeen views are the main icons (A). These allow navigation between the main views, which are: User home view, projects view and templates view. Icons in B, also accessible from all views, are related to administrative tasks, namely \u201cUser and groups management\u201d, current user \u201cProfile\u201d management, \u201cConnection\u201d icon, and access to \u201cHelp\u201d. Breadcrumb (C) allows locating the current project in the global hierarchy. In D are the general element to identify the project, \u201cName\u201d and \u201cDescription\u201d. E contains sub view of the project, which are the \u201cGeneral\u201d view (the one currently displayed), \u201cFiles\u201d (represented in the F view overlaid on the figure), \u201cAnnotations\u201d, which contain the details of each annotations displayed in G. \u201cProperties\u201d and \u201cManagement\u201d allow the management of user permissions and other technicalities (project acronym, template identifier). The (G) table in the File view shows the annotation values or each sample. Table H lists the project characteristics: In (I) are the \u201cPrint\u201d and \u201cExport\u201d icons, which are common to each table. Actions (J) icons allow global action on the current project, such as \u201cPrint\u201d, \u201cNew Project\u201d, \u201cEdit\u201d, \u201cCopy project as Template\u201d, \u201cCopy into the Clipboard\u201d, and \u201cClear Clipboard\u201d.\n\n\n\nAnnotations can be either typed within the Djeen interface or imported from preformatted CSV files. Direct annotation entry is facilitated with an integrated advanced table formatting tool. Multiple data files can also be imported at once (using zip or tar archives) and default annotation values specified to speed up data entry. In a set of annotations, the variables that represent the biological question can be flagged to explicitly mark the datasets that could potentially be integrated since they address similar biological question.\n\nResults and discussion \nTo demonstrate Djeen functionalities and purpose, we describe a detailed microarray importation and management procedure for a microarray dataset of breast cancer patients annotated with clinical conditions. While this specific example is concerned with microarrays, it is also easily applicable to other data types. Specific tutorials detailing management of microarray and flow cytometry data are accessible from the Djeen documentation. The dataset used in the current example[16] is publicly available from the Gene Expression Omnibus (NCBI GEO, http:\/\/www.ncbi.nlm.nih.gov\/\u200bgeo) under the accession number \u201cGSE7390\u201d This dataset spans 198 CEL files, each of them corresponding to a single breast cancer tumor sample. To be able to enforce annotation format and keep consistency among projects, we set up a template for sample annotation that can be re-used by other projects. This project will be part of a hierarchy and defined as a sub-project of a general \u201cBreast Cancer\u201d project. This allows the future inclusion of other projects at the same level within Djeen.\n\nPreparing the project hierarchy within Djeen \nFirst, the data must be stored at the appropriate location within Djeen. This depends on the local organization of data as well as on the studied data type. In all cases, careful consideration of the adopted hierarchy must be taken. For our own purpose, we will create a meta project \u201cbreast cancer\u201d and then a sub project \u201cDesmedt et al. Local Copy\u201d for the data at hand. This is done by clicking on the general tab \u201cProjects\u201d. By using the add button (\u201c+\u201d), a new meta-project called \u201cMeta_Breast_Cancer_Transcriptome\u201d can be added. Dataset description can be filled here, for instance \u201cMeta Breast Cancer Transcriptome project grouping multiple datasets\u201d. Permissions can be specified to limit access to the data. Since this is a publicly available dataset, it can be shared with people already registered to the system. All changes are saved by clicking on the \u201cSave\u201d button.\nSimilarly, a sub-project is being defined to store and describe the data. This is done by clicking the \u201csub-project\u201d tab, creating a new project called \u201cGSE7390 (Desmedt et al.)\u201d. No template is being defined at this point. Again, a description can be added as free text. Permissions are also left to their default settings: access to registered users. Again, changes are saved by a click on \u201cSave\u201d.\nThe previous steps generate the following project hierarchy: \u201cMeta_Breast_Cancer_Transcriptome'->'GSE7390\u201d\n\nImporting microarray data (CELs files) \nThe full test dataset can be directly downloaded from the Gene Expression Omnibus database using the accession number GSE7390. After downloading the full archive, all CEL files are imported within Djeen by a click on the \u201cFile\u201d Icon under the \u201cGSE7390\u201d project. Djeen has a built-in on-the-fly decompression capability for direct importing of tar, tar.gz and zip files.\nAfter importation, all files are accessible from the \u201cFile\u201d tab.\n\nAdding and formatting a MIAME-compliant transcriptome template \nAt this step, a MIAME-compliant template will be applied on the data. This template has two purposes. First, it allows a project administrator to insure that the data is MIAME compliant and second, it allows re-using the same annotations for other datasets.\nTemplates are added from the Template section of Djeen. For our example, it will be named \u201cBreast Cancer Transcriptome Template\u201d. Keywords can be specified as follows: \u201cTranscriptome Breast Cancer Clinical Data\u201d. The description can be specified as 'Template for describing microarray of breast cancer samples'. Changes are saved in the system by a click on \u201cSave\u201d.\nThen, the two template key elements must be populated: Characteristics (variables specific to the dataset) and Annotations (variables specific to samples). In our case, the Characteristics are: \u201cAuthor\u201d, \u201cOriginal GEO\/ArrayExpress Accession Number\u201d, \u201cOrganism\u201d, \u201cPlatform Vendor\u201d and \u201cPlatform Type\u201d.\nValues list and description can be added if necessary. Similarly, Annotations are populated as specified Figure 4. \u201ce.dmfs\u201d and \u201ct.dmfs\u201d are marked as \u201cExperimental Question\u201d.\n\n\n\n\n\n\n\n\n\n Figure 4. Template Edition Interface. This figure shows the template edition view. It allows for editing the list of annotations and their corresponding values for a template. Two mechanisms have been set up to control values that are allowed for a given annotation. If a default value is specified, this value will be set up by default when importing data if no other data is mentioned. Otherwise, a list of values can be specified, to limit the range of possible data. When importing data, the first value will be specified by default if no other data is specified. All metadata (characteristics and annotations) are edited with a similar interface.\n\n\n\nNext, the \u201cBreast Cancer Transcriptome Template\u201d must be linked to the \u201cGSE7390 (Desmedt et al.)\u201d project. This is done from the project view by editing the template field. Once done, 5 Characteristics and 6 Annotation(s) were added to the project.\nThe final step is to populate Characteristics and Annotations. The project contains 198 samples, making the process of manual annotation very lengthy. To ease the process, we wrote an annotation file that can be imported directly within Djeen (available from Djeen documentation page at http:\/\/sourceforge.net\/\u200bprojects\/\u200bdjeen\/\u200bfiles). However, it has to be formatted to be imported, especially to fit the sample database Ids.\nThis is done by generating an empty annotation file by exporting current file annotation data using \u201cFiles\u201d-> \u201cSave the file to annotation.txt\u201d, and editing \u201cannotation.txt\u201d with a spreadsheet and importing data from the \u201cDesmedt-annotations.txt\u201d file contained in the Affymetrix.zip archive.\nThis file can then be imported directly with Djeen by the \u2018Import\u2019 and \u2018Save\u2019 functions. The following message should appear: 198 file(s) correctly edited - 3168 file annotation(s) updated. At this point, the project has been correctly annotated. The annotation structure can be reused in other datasets if necessary.\nThe last step consists in setting up proper permissions to share datasets. Read and Edition parameters can be set from the Permission tab. Also, specific Read and Edition parameters can be set for user groups.\nThe project is now completely loaded within Djeen and can be further edited and shared. Data can then be downloaded from Djeen. Individual samples can be downloaded from the \u201cFile\u201d tab while the whole dataset can be downloaded by performing a snapshot and downloading the resulting archive.\n\nConclusion \nDjeen is a new Research Information Management System designed to answer laboratories' growing needs for flexibility in data management. It allows the sharing, secure storing and annotation of heterogeneous data types, streamlines repetitive annotations tasks and features import functions. Djeen organizes projects within a natural hierarchy similar to files and folders organization on disk. Templates (optionally used) allow automation and MI Information. These features were demonstrated in this report with the demonstration of a real use case for microarray data.\nDjeen features a user-friendly installation procedure and web interface. It is conceived as a Joomla! component, has a fast learning curve and can be deployed over MySQL or PostgreSQL.\nFuture development include setting up an advanced interface for data requests, a scripting module to perform data processing directly from the UI, and an advanced authentication system using LDAP.\n\nAvailability and requirements \nProject name: Database for Joomla!\u2019s Extensible Engine\nProject home page: https:\/\/sourceforge.net\/projects\/djeen\nOperating system(s): Platform independent\nProgramming language: PHP\/Javascript\/SQL\/Perl\nOther requirements: A Linux server running Apache2\/Perl 5.x\/\/PHP 5.3+\/MySQL or PostgreSQL\nLicense: CeCILL\nAny restrictions to use by non-academics: Please contact directly the authors for additional information.\n\nAbbreviations \nCMS: Content Management System\nEULA: End-user license Agreement\nDjeen: Database for Joomla!\u2019s Extensible Engine\nRIMS: Research Information Management System\nMI: Minimum Information\nMIAME: Minimum Information About A Microarray Experiment\nUI: User Interface\n\nDeclarations \nAcknowledgements \nWe would like to thank Dr Fran\u00e7oise Birg and Wahiba Gherraby for their valuable comments on the manuscript. We would also thank the Marseille proteomics core for their involvement.\n\nFunding \nThis project has been funded by an Institut National du Cancer\/Institut National de la sant\u00e9 et de la Recherche M\u00e9dicale grant to G.B. Additional support for Olivier Stahl was obtained from Aix-Marseille University and from the Cancerop\u00f4le Provence-Alpes-C\u00f4te d\u2019Azur. The Djeen server is funded by a Fondation pour la Recherche M\u00e9dicale grant to G.B. and currently maintained by the Datacentre for IT and Scientific Computing of CRCM. Support for Hugo Duvergey is given partly by the R\u00e9gion Languedoc-Roussillon (GEPETOS 2007 contract). OV is supported by the Centre National de la Recherche Scientifique.\n\nCompeting interests \nAuthors declare that they have no competing interests.\n\nAuthors\u2019 contributions \nOS designed the database scheme, software architecture and implemented the web interface and database. He also wrote the manuscript. HD developed installation procedure, finalized code for release and wrote documentation. AG designed import\/export functions. FB and ADV contributed the UI (projects and file views). PF provided initial discussions in interface and microarray data management. SG and OV designed data and template models and provided helpful suggestions. GB funded the project, wrote documentation and finalized the manuscript. All authors participated to debug and release the 1.5 version. All authors read and approved the final manuscript.\n\nReferences \n\n\n\u2191 Bidaut, G.; Stoeckert, C.J. Jr. (2009). \"Characterization of unknown adult stem cell samples by large scale data integration and artificial neural networks\". Pacific Symposium on Biocomputing 14: 356-367. PMID 19209714. http:\/\/psb.stanford.edu\/psb-online\/proceedings\/psb09\/abstracts\/2009_p356.html .   \n\n\u2191 Brazma, A.; Hingamp, P.; Quackenbush, J. et al. (2001). \"Minimum information about a microarray experiment (MIAME)-toward standards for microarray data\". Nature Genetics 29 (4): 365-71. doi:10.1038\/ng1201-365. PMID 11726920.   \n\n\u2191 Lee, J.A.; Spidlen, J.; Boyce, K. et al. (2008). \"MIFlowCyt: the minimum information about a Flow Cytometry Experiment\". Cytometry Part A 73 (10): 926-30. doi:10.1002\/cyto.a.20623. PMC PMC2773297. PMID 18752282. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2773297 .   \n\n\u2191 Binz, P.-A.; Barkovich, R.; Beavis, R.C.; Creasy, D.; Horn, D.M.; Julian, R.K.; Seymour, S.L.; Taylor, C.F.; Vandenbrouck, Y. (2008). \"Guidelines for reporting the use of mass spectrometry informatics in proteomics\". Nature Biotechnology 26 (8): 862. doi:10.1038\/nbt0808-862. PMID 18688233.   \n\n\u2191 5.0 5.1 Killion, P.J.; Iyer, V.R. (2004). \"Microarray data visualization and analysis with the Longhorn Array Database (LAD)\". Current Protocols in Bioinformatics 7.10. doi:10.1002\/0471250953.bi0710s08. PMID 18428730.   \n\n\u2191 6.0 6.1 Vallon-Christersson, J.; Nordborg, N.; Svensson, M.; H\u00e4kkinen, J. (2009). \"BASE - 2nd generation software for microarray data management and analysis\". BMC Bioinformatics 10: 330. doi:10.1186\/1471-2105-10-330. PMC PMC2768720. PMID 19822003. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2768720 .   \n\n\u2191 7.0 7.1 Helsens, K.; Colaert, N.; Barsnes, H. et al. (2010). \"ms_lims, a simple yet powerful open source laboratory information management system for MS-driven proteomics\". Proteomics 6 (10): 1261\u20131264. doi:10.1002\/pmic.200900409. PMID 20058248.   \n\n\u2191 Tai, D.; Chaguturu, R; Fang, J. (2011). \"K-Screen: A free application for high throughput screening data analysis, visualization, and laboratory information management\". Combinatorial Chemistry & High Throughput Screening 14 (9): 757-65. doi:10.2174\/138620711796957116. PMID 21631412.   \n\n\u2191 Myneni, S.; Patel, V.L. (2010). \"Organization of Biomedical Data for Collaborative Scientific Research: A Research Information Management System\". International Journal of Information Management 30 (3): 256-264. doi:10.1016\/j.ijinfomgt.2009.09.005. PMC PMC2882303. PMID 20543892. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2882303 .   \n\n\u2191 Russom, D.; Ahmed, A.; Gonzalez, N.; Alvarnas, J.; DiGiusto, D. (2012). \"Implementation of a configurable laboratory information management system for use in cellular process development and manufacturing\". Cytotherapy 14 (1): 114-21. doi:10.3109\/14653249.2011.619007. PMID 21973024.   \n\n\u2191 Lin, K.; Kools, H.; de Groot, P.J. et al. (2011). \"MADMAX - Management and analysis database for multiple omics experiments\". Journal of Integrative Bioinformatics 8 (2): 160. doi:10.2390\/biecoll-jib-2011-160. PMID 21778530.   \n\n\u2191 Melo, A.; Faria-Campos, A.; DeLaat, D.M.; Keller, R.; Abreu, V.; Campos, S. (2010). \"SIGLa: an adaptable LIMS for multiple laboratories\". BMC Genomics 11 (Suppl 5): S8. doi:10.1186\/1471-2164-11-S5-S8. PMC PMC3045801. PMID 21210974. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3045801 .   \n\n\u2191 Bath, T.G.; Bozdag, S.; Afzal, V.; Crowther. D. (2011). \"LimsPortal and BonsaiLIMS: development of a lab information management system for translational medicine\". Source Code for Biology and Medicine 6: 9. doi:10.1186\/1751-0473-6-9. PMC PMC3113716. PMID 21569484. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3113716 .   \n\n\u2191 14.0 14.1 Mooney, S.D.; Baenziger, P.H. (2008). \"Extensible open source content management systems and frameworks: a solution for many needs of a bioinformatics group\". Briefings in Bioinformatics 9 (1): 69-74. doi:10.1093\/bib\/bbm057. PMID 18057072.   \n\n\u2191 Leff, A.; Rayfield, J.T. (2001). \"Web-application development using the Model\/View\/Controller design pattern\". Proceedings Fifth IEEE International Enterprise Distributed Object Computing Conference: 118-127. doi:10.1109\/EDOC.2001.950428.   \n\n\u2191 Desmedt, C.; Haibe-Kains, B.; Wirapati, P.; Buyse, M.; Larsimont, D.; Bontempi, G.; Delorenzi, M.; Piccart, M.; Sotiriou, C. (2008). \"Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes\". Clinical Cancer Research 14 (16): 5158-65. doi:10.1158\/1078-0432.CCR-07-4756. PMID 18698033.   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. In one case a direct reference to a citation number was changed to reference the author names instead.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Djeen_(Database_for_Joomla!%E2%80%99s_Extensible_Engine):_A_research_information_management_system_for_flexible_multi-technology_project_administration\">https:\/\/www.limswiki.org\/index.php\/Journal:Djeen_(Database_for_Joomla!%E2%80%99s_Extensible_Engine):_A_research_information_management_system_for_flexible_multi-technology_project_administration<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on bioinformaticsLIMSwiki journal articles on software\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 11 January 2016, at 23:53.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 1,887 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","8552328b588cc33465f115d2b29dced0_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_Djeen_Database_for_Joomla_\u2019s_Extensible_Engine_A_research_information_management_system_for_flexible_multi-technology_project_administration skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Djeen (Database for Joomla!\u2019s Extensible Engine): A research information management system for flexible multi-technology project administration<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p><b>Background<\/b>: With the advance of post-genomic technologies, the need for tools to manage large scale data in biology becomes more pressing. This involves annotating and storing data securely, as well as granting permissions flexibly with several technologies (all array types, flow cytometry, proteomics) for collaborative work and data sharing. This task is not easily achieved with most systems available today.\n<\/p><p><b>Findings<\/b>: We developed Djeen (Database for Joomla!\u2019s Extensible Engine), a new Research Information Management System (RIMS) for collaborative projects. Djeen is a user-friendly application, designed to streamline data storage and annotation collaboratively. Its database model, kept simple, is compliant with most technologies and allows storing and managing of heterogeneous data with the same system. Advanced permissions are managed through different roles. Templates allow Minimum Information (MI) compliance.\n<\/p><p><b>Conclusion<\/b>: Djeen allows managing project associated with heterogeneous data types while enforcing annotation integrity and minimum information. Projects are managed within a hierarchy and user permissions are finely-grained for each project, user and group.\n<\/p><p>Djeen Component source code (version 1.5.1) and installation documentation are available under CeCILL license from <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/sourceforge.net\/projects\/djeen\/files\" target=\"_blank\">http:\/\/sourceforge.net\/projects\/djeen\/files<\/a> and supplementary material.\n<\/p><p><b>Keywords<\/b>: Database, CMS, Minimum Information, RIMS\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Findings\">Findings<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Background\">Background<\/span><\/h3>\n<p>Advent of post-genomic era has seen a massive adoption of technologies that fundamentally changed the way biological assays are designed, data generated and collected, and further analyzed. Typical biological\/genomic projects are now involving geographically spread <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" target=\"_blank\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratories<\/a> that conduct large scale experiments that need to be analyzed in an integrated way.<sup id=\"rdp-ebb-cite_ref-BidautChar09_1-0\" class=\"reference\"><a href=\"#cite_note-BidautChar09-1\" rel=\"external_link\">[1]<\/a><\/sup> Data must therefore be thoroughly annotated and mutually shared with fine-grained user permissions. It is also crucial that data annotation meet Minimum Information (MI) as well as standards defined in the lab where these data were generated. MI standards have been initially defined for microarray experiments (MIAME)<sup id=\"rdp-ebb-cite_ref-BrazmaMin01_2-0\" class=\"reference\"><a href=\"#cite_note-BrazmaMin01-2\" rel=\"external_link\">[2]<\/a><\/sup> and have since been extended to other technologies, including flow cytometry (MIFlowCyt)<sup id=\"rdp-ebb-cite_ref-LeeMIFlow08_3-0\" class=\"reference\"><a href=\"#cite_note-LeeMIFlow08-3\" rel=\"external_link\">[3]<\/a><\/sup> and proteomics (MIAPE).<sup id=\"rdp-ebb-cite_ref-BinzGuide08_4-0\" class=\"reference\"><a href=\"#cite_note-BinzGuide08-4\" rel=\"external_link\">[4]<\/a><\/sup>\n<\/p><p>Several <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" target=\"_blank\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">Laboratory Information Management Systems<\/a> (LIMS) have been created over the years. Even though these have proven usefulness in instruments everyday usage, increasing data integration needs have underlined typical LIMS drawbacks in most laboratories.\n<\/p><p>Firstly, LIMS are usually conceived to manage data issued from a single technology type, such as DNA microarray<sup id=\"rdp-ebb-cite_ref-KillionMicro04_5-0\" class=\"reference\"><a href=\"#cite_note-KillionMicro04-5\" rel=\"external_link\">[5]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-VallonBASE09_6-0\" class=\"reference\"><a href=\"#cite_note-VallonBASE09-6\" rel=\"external_link\">[6]<\/a><\/sup>, proteomics<sup id=\"rdp-ebb-cite_ref-Helsens_ms10_7-0\" class=\"reference\"><a href=\"#cite_note-Helsens_ms10-7\" rel=\"external_link\">[7]<\/a><\/sup>, high throughput sequencing.<sup id=\"rdp-ebb-cite_ref-TaiK-Screen11_8-0\" class=\"reference\"><a href=\"#cite_note-TaiK-Screen11-8\" rel=\"external_link\">[8]<\/a><\/sup> This complicates further data integration and analysis since separate data types are typically stored on separate LIMS.\n<\/p><p>Secondly, any data evolution or reorganization implies re-engineering and adopting a new LIMS. Most LIMS rather meet lab requirements at a given instant without taking into account the fact that technology, data formats, structures and devices are constantly changing and evolving, which restrains long-term use of the system.\n<\/p><p>Finally, each additional device installed in the laboratory implies training users on new laboratory practices since all LIMS are designed with different user interfaces (UIs). Subsequent fragmentation of systems and resources has a negative impact on quality control (QC). Moreover, administrating heterogeneous LIMS is a complex task that cannot be assumed by a typical wet laboratory structure that does not have the <a href=\"https:\/\/www.limswiki.org\/index.php\/Bioinformatics\" title=\"Bioinformatics\" target=\"_blank\" class=\"wiki-link\" data-key=\"8f506695fdbb26e3f314da308f8c053b\">bioinformatics<\/a> expertise and development resources to adapt tools to its specific needs. Because of these limits, typical LIMS do not favor interdisciplinary and translational collaborations and thus prevent the transfer of knowledge among laboratories generating heterogeneous information that has to be integrated.\n<\/p><p>In this report, we describe the Database for <a href=\"https:\/\/www.limswiki.org\/index.php\/Joomla\" title=\"Joomla\" target=\"_blank\" class=\"wiki-link\" data-key=\"54d4eaf93f0364a2d47e52976b99e32d\">Joomla!<\/a>\u2019s Extensible Engine (Djeen), a new generation of LIMS that features a simple technological conception coupled with an advanced capacity of adaptation to be directly used or easily adapted to different technologies. The Djeen database scheme is kept simple to maximize generalization and application possibilities. Only data organization and metadata (annotations) are stored within a database, while experimental data is organized in the file system. In addition, the program is adaptable to any technology since no technology-dependent semantics were used in the code. Djeen can therefore evolve with user and laboratory needs. Since most technology can be managed with Djeen, this allows for unification of all information systems within the lab.\n<\/p><p>Djeen features a large functionality set (import\u2013export, multi-technological implementation, advanced user\/groups permissions) and is conceptually more advanced than other LIMS publicly available. Djeen qualifies as a Research Information Management System.<sup id=\"rdp-ebb-cite_ref-MyneniOrg10_9-0\" class=\"reference\"><a href=\"#cite_note-MyneniOrg10-9\" rel=\"external_link\">[9]<\/a><\/sup> As such, Djeen addresses four fundamental issues in high throughput biomedical data management: data organization, data sharing, collaboration and publication.\n<\/p><p>Data organization consists in allowing straightforward data retrieval without the presence of the person who generated them. Therefore, data must be securely stored in a standardized way.\n<\/p><p>Data sharing consists in allowing several collaborators to access the same data, while avoiding data duplication or data reformatting. Collaboration is an important aspect of dataset entry and development; it allows several collaborators to manage and maintain the same data, which means that the data is not organized by a single individual. Finally, data publication encompasses secure data sharing for a large group of users (over the Internet or intranet).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Related_work\">Related work<\/span><\/h3>\n<p>Many LIMS have been developed by large companies to respond to precise specifications responding to needs by a given laboratories. There exists also generic commercial LIMS that can be customized to specific needs. Some of them were confronted to a real situation in a large cell production facility.<sup id=\"rdp-ebb-cite_ref-RussomImp12_10-0\" class=\"reference\"><a href=\"#cite_note-RussomImp12-10\" rel=\"external_link\">[10]<\/a><\/sup> In this paper, all facility members compared several LIMS according to multiple criteria and adopted a commercial LIMS. A consultant was hired for one year to adapt the LIMS to their specific needs, and adapt other modules, which implies significant means. On the contrary, Djeen was conceived to be used by small research groups with no or little dedicated bioinformatics support and few resources.\n<\/p><p>A commercial LIMS is hence not a \u2018ready to use\u2019 program and necessitate a very complex installation specific to end-user usage. Also, there is a strong dependence on the software\u2019s vendor and his ability to follow up on the product and insure longevity, which is not guaranteed. Djeen being open source and under CeCILL license, anyone can contribute to it and it will stay available.\n<\/p><p>A number of publicly available open source LIMS exist, and partially addressed the issues described in this paper. Many LIMS are inherently limited to a single technology type, i.e. Proteomics (ms_lims<sup id=\"rdp-ebb-cite_ref-Helsens_ms10_7-1\" class=\"reference\"><a href=\"#cite_note-Helsens_ms10-7\" rel=\"external_link\">[7]<\/a><\/sup>) or microarray (BASE<sup id=\"rdp-ebb-cite_ref-VallonBASE09_6-1\" class=\"reference\"><a href=\"#cite_note-VallonBASE09-6\" rel=\"external_link\">[6]<\/a><\/sup>, or the Longhorn Array Database<sup id=\"rdp-ebb-cite_ref-KillionMicro04_5-1\" class=\"reference\"><a href=\"#cite_note-KillionMicro04-5\" rel=\"external_link\">[5]<\/a><\/sup>), which is a serious limitation for many laboratories, who need the same system to store all their data. Djeen allows for managing heterogeneous datasets within the same system.\n<\/p><p>Other LIMS can be used to manage multiple technologies. MADMAX<sup id=\"rdp-ebb-cite_ref-LinMAD11_11-0\" class=\"reference\"><a href=\"#cite_note-LinMAD11-11\" rel=\"external_link\">[11]<\/a><\/sup> allows for the storage and analysis of heterogeneous genomics data in the same repository. However, its implementation is rather complex and based on an Oracle (Redwood City, CA, USA) Database Management System (DBMS), which can be a limiting factor for some laboratories with limited resources. Djeen is based solely on open-source technology, being its database (<a href=\"https:\/\/www.limswiki.org\/index.php\/MySQL\" title=\"MySQL\" target=\"_blank\" class=\"wiki-link\" data-key=\"35005451bfcd508bce47c58e72260128\">MySQL<\/a> or <a href=\"https:\/\/www.limswiki.org\/index.php\/PostgreSQL\" title=\"PostgreSQL\" target=\"_blank\" class=\"wiki-link\" data-key=\"a5dd945cdcb63e2d8f7a5edb3a896d82\">PostgreSQL<\/a>) or the Content Management System (Joomla!). <a href=\"https:\/\/www.limswiki.org\/index.php\/SIGLa\" title=\"SIGLa\" target=\"_blank\" class=\"wiki-link\" data-key=\"79f61f131c17669ec4b1f7e0e7547e92\">SIGLa<\/a> (Systema Integrado de Ger\u00eancia de Laboratori\u00f3s<sup id=\"rdp-ebb-cite_ref-12\" class=\"reference\"><a href=\"#cite_note-12\" rel=\"external_link\">[12]<\/a><\/sup>) is based on a workflow management tool that makes it also adaptable to multiple usages. The concept of workflows is not needed by all users and increases dramatically the complexity of data entry. Therefore, workflows are not hard-coded into Djeen to avoid technology-specific code but can be used with annotations when needed.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/BonsaiLIMS\" title=\"BonsaiLIMS\" target=\"_blank\" class=\"wiki-link\" data-key=\"e477f6b8a042bd8703a30ef83dbcd0c9\">BonsaiLIMS<\/a><sup id=\"rdp-ebb-cite_ref-BathLims11_13-0\" class=\"reference\"><a href=\"#cite_note-BathLims11-13\" rel=\"external_link\">[13]<\/a><\/sup> is a lightweight LIMS developed initially to centralize patient records for translational research. However, BonsaiLIMS features only a very limited model and functionality set as compared to Djeen, which works \u201cout of the box\u201d after a deployment from the Joomla!\u2019s component deployment interface. Djeen features more functionality, such as templates group permission management and data export.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Implementation\">Implementation<\/span><\/h3>\n<p>Djeen is a Research Information Management System developed to meet the four type of functionalities described above:\n<\/p><p><i>Data organization<\/i>\n<\/p><p>Djeen structures data into a hierarchical system allowing creating and managing complex data structures hierarchically with high flexibility while enforcing standardization and Minimum information standards. Djeen is able to manage projects containing heterogeneous data types while maintaining homogeneous annotations through the optional use of templates.\n<\/p><p><i>Data sharing<\/i>\n<\/p><p>Data is shared through fine-grained user permissions to strengthen data security. Several user roles are defined and granted with gradually increasing permissions. This allows managing data that is completely confidential as well as sharing it with specified users and groups, or release it publicly over the Internet.\n<\/p><p><i>User collaboration<\/i>\n<\/p><p>User collaboration goes beyond data sharing. It implies that datasets are built and contributed to by several collaborators while general project structure and annotations are under the control of a project owner. In Djeen, once permissions are set to appropriate users or groups, project administrators can control homogeneity of annotations with templates. Templates allow enforcing data integrity and homogeneity as well as quality control (QC). Their role is detailed in the \u2018Data organization and Djeen elements\u2019 section.\n<\/p><p><i>Publication<\/i>\n<\/p><p>To be able to publish datasets and meet needs for data sharing and collaborations, Djeen was developed as a Web application.\n<\/p><p><i>Djeen software administration<\/i>\n<\/p><p>A fifth item was taken into account when designing Djeen. Djeen was conceived as a Web application that is simple to install, easy to learn and to administrate. A Djeen instance is maintainable by a research group with no or little dedicated bioinformatics human resources, and usable with a minimal training.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Content_management_system\">Content management system<\/span><\/h3>\n<p>Djeen was developed as an extension of the Joomla! Content Management System (CMS).\n<\/p><p>CMS are a category of applications allowing the management and the publication of content, \u201ccontent\u201d being defined rather loosely (see Mooney and Baenziger<sup id=\"rdp-ebb-cite_ref-MooneyExt08_14-0\" class=\"reference\"><a href=\"#cite_note-MooneyExt08-14\" rel=\"external_link\">[14]<\/a><\/sup> for a review of CMS usage in bioinformatics). In our case, it is related to scientific <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" target=\"_blank\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a>, and more precisely, data and their annotations. CMS are very attractive since they are characterized by a modular design and allow for development of new applications for visualizing content. Reuse of CMS tools for web application development potentially simplifies things and allows programmers to focus on the application features instead of spending time on redeveloping a number of generic functionalities, such as site administration and visual design.\n<\/p><p>As compared to a home grown development, developing a web application as a CMS extension allowed us to maximize the security by taking advantage of the existing authentication system. Additionally, security does not depend entirely on the application itself but also on the local network configuration.\n<\/p><p>The appropriate choice for a CMS is crucial especially considering security issues.<sup id=\"rdp-ebb-cite_ref-MooneyExt08_14-1\" class=\"reference\"><a href=\"#cite_note-MooneyExt08-14\" rel=\"external_link\">[14]<\/a><\/sup> We carefully choose the CMS on several criteria, including active support, presence of a documented API, quality of the interface in terms of look and feel, and simplicity of administration and installation. In regard to all these considerations, we decided to develop Djeen as a Joomla! 1.5 component.\n<\/p><p>Joomla! version 1.5 is an open-source Content Management System (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.joomla.org\" target=\"_blank\">http:\/\/www.joomla.org<\/a>) featuring a documented API to create advanced extensions based on a Model-View-Controller (MVC) Design Pattern.<sup id=\"rdp-ebb-cite_ref-LeffWeb01_15-0\" class=\"reference\"><a href=\"#cite_note-LeffWeb01-15\" rel=\"external_link\">[15]<\/a><\/sup> Additionally, it is backed-up by a large community of developers that quickly releases security patches and new versions and update documentation.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Integration_within_the_Joomla.21_CMS\">Integration within the Joomla! CMS<\/span><\/h4>\n<p>To understand how Djeen interacts with Joomla!, a summary of its architecture and function is given. As shown in Figure 1, Joomla! was conceived as a three tier system based on this MVC structure, to separate data access (Models), rendering system (Views) and actions (Controllers).\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Stahl_BMCResearchNotes2013_6.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"c484042a1ee0acd9571dbfa5b8b3255f\"><img alt=\"Fig1 Stahl BMCResearchNotes2013 6.jpg\" src=\"https:\/\/www.limswiki.org\/images\/b\/b0\/Fig1_Stahl_BMCResearchNotes2013_6.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 1. Joomla! API and Djeen implementation.<\/b> This figure shows the Joomla's API and the mechanisms of interaction between Djeen and Joomla!. The right part of the figure represents the three tiered Joomla! API (adapted from Joomla's documentation, (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/docs.joomla.org\/\u200bFramework\/\u200b1.\u200b5#Packages_\u200band_\u200bClasses\" target=\"_blank\">http:\/\/docs.joomla.org\/\u200bFramework\/\u200b1.\u200b5#Packages_\u200band_\u200bClasses<\/a>). This architecture defines the software from data access to the final application display through a Model-View-Controller (MVC) model. The left part of the figure shows specific Djeen main components (Djeen database, file repository) as well as Joomla!'s components (Joomla!'s database, containing user information and component configuration) reused by Djeen. Djeen uses the framework layer to interact with Joomla! and manages users\u2019 connections and the application layer for display.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>The purpose of the framework layer is to manage data within Joomla!, it includes different classes and libraries to access database and file system. The application layer manages Joomla!'s UI, such as administration panel and public website. Finally, the extension layer includes templates to change the website rendering and extensions to change or extend Joomla!'s functionalities. Modules are used to display additional data bits and pieces into specific \u2018boxes\u2019. Components are a more advanced type of extensions that allow developing full fledged applications while granted access to the Joomla! API. Djeen is a Component and implements its own database and a dedicated repository.\n<\/p><p>By using the Joomla! API, Djeen is deployed and managed from the Joomla! administrator panel. No third party software or client is needed and compatibility was validated on the Mozilla Firefox\u00ae and Google Chrome\u00ae browsers (current versions as of publication). The application is embedded to the Joomla! front-end website through the application layer.\n<\/p><p>Data security is ensured by a complete separation of Djeen and Joomla! databases to facilitate backup and keeping Djeen as an independent component at every level. Djeen objects are stored within a specific relational database (PostgreSQL and MySQL drivers are provided) while files are simply stored in the file system. The connection to the Djeen external database is ensured by a second security level that uses an encrypted password stored into the component configuration. Several databases can be maintained, and each instance has its own password.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Data_organization_and_Djeen_elements\">Data organization and Djeen elements<\/span><\/h4>\n<p>In this section, Djeen objects (such as Projects and Templates) are refereed to with a capital letter. These are simply referred to as generic terms in subsequent sections.\n<\/p><p>Figure 2 shows the Djeen data model main elements and the duality files-database. The File object is the central piece of information within Djeen, since it represents the lowest granularity level in most high-throughput analyses. This model and the associated code were designed to be technology-independent and free of specific semantics to stay adaptable to multiple data types and as generalizable as possible. In the database side, the main Djeen entity to manage data is the Project. Projects are organized in a hierarchy and a Project can reference multiple sub-Projects. This hierarchy is mirrored in the corresponding directory organization on the file system side. Projects are linked to Files issued from experimentation or analysis using this directory organization. Projects are equivalent to folders and files are simply stored within these folders. This organization is very intuitive and simple to manage and backup.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Stahl_BMCResearchNotes2013_6.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"7e53a4e93d805db2b2e481c8be874a76\"><img alt=\"Fig2 Stahl BMCResearchNotes2013 6.jpg\" src=\"https:\/\/www.limswiki.org\/images\/3\/38\/Fig2_Stahl_BMCResearchNotes2013_6.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 2. Djeen data organization model.<\/b> Djeen separates Projects hierarchy, Templates and Annotations on one side (these are stored in the Djeen relational database) and the data itself (stored in the file system). Data stored into the database are divided into several objects, each of them being represented by a database table, linked to a class model in the MVC architecture. Project is the primary Djeen organizational element. It allows the construction of a hierarchical tree of sub-Projects and includes metadata about itself and stored files. The File object is the most basic and central piece of information within Djeen, since it represents the lowest granularity level in most high-throughput analyses. This project\/files hierarchical tree is structurally mirrored into the file system. Metadata are divided into Characteristics (related to Projects) and Annotations (related to Files). Those two types of metadata can be saved into Templates, allowing users to reuse them into other Projects. The Users object is a specific table containing user and group information. It supersedes the Joomla! system by formation specific to Djeen that allows managing specific permissions and groups while permitting reuse of all the features already implemented in the CMS, such as authentication or e-mailing.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>Files and Projects are annotated by two types of metadata. The Annotations are related to Files and the Characteristics are specifically related to Projects. Annotations contain sample or condition-specific information while Characteristics contain general Project information and descriptions.\n<\/p><p>To allow reusing metadata for similar Projects, Templates were introduced. They allow storing a predefined list of Annotations and Characteristics that will be used when creating a Project. Templates have specific owners and cannot be modified once they are used in a Project to prevent further unwanted modifications.\n<\/p><p>No constrains are imposed by Djeen implementation on Project structure or Annotations types. This allows for the use of multiple data types in the same management system. However, Projects manager can optionally use Templates to enforce the type of Annotations to be provided by the experimentalist and enforce MI compliance if necessary. Data provenance, for instance, can be encoded as a mandatory annotation field. Templates also allow structuring the Project, to permit further data integration and promote QC by being consistent with MI and sample annotations. In addition to Templates and Annotations, Djeen allows highlighting (with a flag) a specific annotation that corresponds to the biological question asked in a Project.\n<\/p><p>Djeen allows data sharing under an advanced permission system that supersedes the native user management system of Joomla! by adding specific information. Four roles have been defined (Superadministrator, Administrator, Moderator, and User) granted with specific permissions on data, User\/Groups and Template management. A given Project is owned by an Administrator or a Moderator who has the role of Project owner. He controls annotations and user permissions on files. Projects and sub-Projects permissions can be granted to specific user groups to finely manage access of large scale collaborative projects.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Web_interface_and_Djeen_functionality\">Web interface and Djeen functionality<\/span><\/h4>\n<p>Djeen\u2019s UI was designed to facilitate navigation and manipulation of data as intuitively as possible and features a fast learning curve. To optimize interoperability with Joomla! and maximize its maintainability, Djeen was mainly developed in PHP. A data uploader was developed in Perl to allow massive data transfers (of several GBs) for importation of large sets of raw data. All table rendering and user interaction code was implemented an Ajax\/Javascript layer through the Mootools library (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/mootools.net\" target=\"_blank\">http:\/\/mootools.net<\/a>). Additionally, a customizable dialog box was made available for administrators to display information such as an End-User License Agreement (EULA) for users, as well as any other information or error messages.\n<\/p><p>The Djeen UI main elements are represented Figure 3. Main icons (A) allow for quick access to projects and experiments and search dialog. Other icons (B) allow for template management, user and group management, current user options, and connection to the system. The breadcrumbs (C) allow for navigating project hierarchy. Panel (D) shows the main project view. It features general description, owner and creation date, template used and characteristics table (H). The tabs (E) allow for management of sub-projects, files, annotations, project history and specific user permissions. The \u201cFiles\u201d tab opens a panel (overlaid here) displaying the list of files linked to the current project (F), annotated using the annotations table (G). Moreover, users can generate snapshots of the whole project by using the \u201cHistory\u201d function in (E). Such a snapshot allows project manager to generate a data freeze for publication of a project. A notification zone displays messages returned by the system (I) in an elegant and non-intrusive manner. (I) icons are functions present in most tables, namely \u201cPrint\u201d and \u201cExport\u201d. Icons (J) are general project actions including \u201cPrint\u201d, \u201cNew Project\u201d, \u201cEdit\u201d, \u201cCopy as template\u201d, \u201cCopy in Clipboard\u201d and \u201cClear Clipboard\u201d.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Stahl_BMCResearchNotes2013_6.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"cd1f911ff3909603e61ca9fd275d6e7b\"><img alt=\"Fig3 Stahl BMCResearchNotes2013 6.jpg\" src=\"https:\/\/www.limswiki.org\/images\/b\/b4\/Fig3_Stahl_BMCResearchNotes2013_6.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 3. Djeen Web Interface.<\/b> This figure shows the Djeen web interface opened on the project view, as seen as connected as a user with read permissions. The web interface is embedded within Joomla! (Not represented here), and presents all elements related to this particular view as well as some elements common to several views. Among the common element to all Djeen views are the main icons (A). These allow navigation between the main views, which are: User home view, projects view and templates view. Icons in B, also accessible from all views, are related to administrative tasks, namely \u201cUser and groups management\u201d, current user \u201cProfile\u201d management, \u201cConnection\u201d icon, and access to \u201cHelp\u201d. Breadcrumb (C) allows locating the current project in the global hierarchy. In D are the general element to identify the project, \u201cName\u201d and \u201cDescription\u201d. E contains sub view of the project, which are the \u201cGeneral\u201d view (the one currently displayed), \u201cFiles\u201d (represented in the F view overlaid on the figure), \u201cAnnotations\u201d, which contain the details of each annotations displayed in G. \u201cProperties\u201d and \u201cManagement\u201d allow the management of user permissions and other technicalities (project acronym, template identifier). The (G) table in the File view shows the annotation values or each sample. Table H lists the project characteristics: In (I) are the \u201cPrint\u201d and \u201cExport\u201d icons, which are common to each table. Actions (J) icons allow global action on the current project, such as \u201cPrint\u201d, \u201cNew Project\u201d, \u201cEdit\u201d, \u201cCopy project as Template\u201d, \u201cCopy into the Clipboard\u201d, and \u201cClear Clipboard\u201d.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>Annotations can be either typed within the Djeen interface or imported from preformatted CSV files. Direct annotation entry is facilitated with an integrated advanced table formatting tool. Multiple data files can also be imported at once (using zip or tar archives) and default annotation values specified to speed up data entry. In a set of annotations, the variables that represent the biological question can be flagged to explicitly mark the datasets that could potentially be integrated since they address similar biological question.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results_and_discussion\">Results and discussion<\/span><\/h2>\n<p>To demonstrate Djeen functionalities and purpose, we describe a detailed microarray importation and management procedure for a microarray dataset of breast cancer patients annotated with clinical conditions. While this specific example is concerned with microarrays, it is also easily applicable to other data types. Specific tutorials detailing management of microarray and flow cytometry data are accessible from the Djeen documentation. The dataset used in the current example<sup id=\"rdp-ebb-cite_ref-DesmedtBio08_16-0\" class=\"reference\"><a href=\"#cite_note-DesmedtBio08-16\" rel=\"external_link\">[16]<\/a><\/sup> is publicly available from the Gene Expression Omnibus (NCBI GEO, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/\u200bgeo\" target=\"_blank\">http:\/\/www.ncbi.nlm.nih.gov\/\u200bgeo<\/a>) under the accession number \u201cGSE7390\u201d This dataset spans 198 CEL files, each of them corresponding to a single breast cancer tumor sample. To be able to enforce annotation format and keep consistency among projects, we set up a template for sample annotation that can be re-used by other projects. This project will be part of a hierarchy and defined as a sub-project of a general \u201cBreast Cancer\u201d project. This allows the future inclusion of other projects at the same level within Djeen.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Preparing_the_project_hierarchy_within_Djeen\">Preparing the project hierarchy within Djeen<\/span><\/h3>\n<p>First, the data must be stored at the appropriate location within Djeen. This depends on the local organization of data as well as on the studied data type. In all cases, careful consideration of the adopted hierarchy must be taken. For our own purpose, we will create a meta project \u201cbreast cancer\u201d and then a sub project \u201cDesmedt et al. Local Copy\u201d for the data at hand. This is done by clicking on the general tab \u201cProjects\u201d. By using the add button (\u201c+\u201d), a new meta-project called \u201cMeta_Breast_Cancer_Transcriptome\u201d can be added. Dataset description can be filled here, for instance \u201cMeta Breast Cancer Transcriptome project grouping multiple datasets\u201d. Permissions can be specified to limit access to the data. Since this is a publicly available dataset, it can be shared with people already registered to the system. All changes are saved by clicking on the \u201cSave\u201d button.\n<\/p><p>Similarly, a sub-project is being defined to store and describe the data. This is done by clicking the \u201csub-project\u201d tab, creating a new project called \u201cGSE7390 (Desmedt et al.)\u201d. No template is being defined at this point. Again, a description can be added as free text. Permissions are also left to their default settings: access to registered users. Again, changes are saved by a click on \u201cSave\u201d.\n<\/p><p>The previous steps generate the following project hierarchy: \u201cMeta_Breast_Cancer_Transcriptome'->'GSE7390\u201d\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Importing_microarray_data_.28CELs_files.29\">Importing microarray data (CELs files)<\/span><\/h3>\n<p>The full test dataset can be directly downloaded from the Gene Expression Omnibus database using the accession number GSE7390. After downloading the full archive, all CEL files are imported within Djeen by a click on the \u201cFile\u201d Icon under the \u201cGSE7390\u201d project. Djeen has a built-in on-the-fly decompression capability for direct importing of tar, tar.gz and zip files.\n<\/p><p>After importation, all files are accessible from the \u201cFile\u201d tab.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Adding_and_formatting_a_MIAME-compliant_transcriptome_template\">Adding and formatting a MIAME-compliant transcriptome template<\/span><\/h3>\n<p>At this step, a MIAME-compliant template will be applied on the data. This template has two purposes. First, it allows a project administrator to insure that the data is MIAME compliant and second, it allows re-using the same annotations for other datasets.\n<\/p><p>Templates are added from the Template section of Djeen. For our example, it will be named \u201cBreast Cancer Transcriptome Template\u201d. Keywords can be specified as follows: \u201cTranscriptome Breast Cancer Clinical Data\u201d. The description can be specified as 'Template for describing microarray of breast cancer samples'. Changes are saved in the system by a click on \u201cSave\u201d.\n<\/p><p>Then, the two template key elements must be populated: Characteristics (variables specific to the dataset) and Annotations (variables specific to samples). In our case, the Characteristics are: \u201cAuthor\u201d, \u201cOriginal GEO\/ArrayExpress Accession Number\u201d, \u201cOrganism\u201d, \u201cPlatform Vendor\u201d and \u201cPlatform Type\u201d.\n<\/p><p>Values list and description can be added if necessary. Similarly, Annotations are populated as specified Figure 4. \u201ce.dmfs\u201d and \u201ct.dmfs\u201d are marked as \u201cExperimental Question\u201d.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_Stahl_BMCResearchNotes2013_6.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"4327ce278fd01966466503a73401dc6f\"><img alt=\"Fig4 Stahl BMCResearchNotes2013 6.jpg\" src=\"https:\/\/www.limswiki.org\/images\/8\/8f\/Fig4_Stahl_BMCResearchNotes2013_6.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 4. Template Edition Interface.<\/b> This figure shows the template edition view. It allows for editing the list of annotations and their corresponding values for a template. Two mechanisms have been set up to control values that are allowed for a given annotation. If a default value is specified, this value will be set up by default when importing data if no other data is mentioned. Otherwise, a list of values can be specified, to limit the range of possible data. When importing data, the first value will be specified by default if no other data is specified. All metadata (characteristics and annotations) are edited with a similar interface.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>Next, the \u201cBreast Cancer Transcriptome Template\u201d must be linked to the \u201cGSE7390 (Desmedt et al.)\u201d project. This is done from the project view by editing the template field. Once done, 5 Characteristics and 6 Annotation(s) were added to the project.\n<\/p><p>The final step is to populate Characteristics and Annotations. The project contains 198 samples, making the process of manual annotation very lengthy. To ease the process, we wrote an annotation file that can be imported directly within Djeen (available from Djeen documentation page at <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/sourceforge.net\/\u200bprojects\/\u200bdjeen\/\u200bfiles\" target=\"_blank\">http:\/\/sourceforge.net\/\u200bprojects\/\u200bdjeen\/\u200bfiles<\/a>). However, it has to be formatted to be imported, especially to fit the sample database Ids.\n<\/p><p>This is done by generating an empty annotation file by exporting current file annotation data using \u201cFiles\u201d-> \u201cSave the file to annotation.txt\u201d, and editing \u201cannotation.txt\u201d with a spreadsheet and importing data from the \u201cDesmedt-annotations.txt\u201d file contained in the Affymetrix.zip archive.\n<\/p><p>This file can then be imported directly with Djeen by the \u2018Import\u2019 and \u2018Save\u2019 functions. The following message should appear: 198 file(s) correctly edited - 3168 file annotation(s) updated. At this point, the project has been correctly annotated. The annotation structure can be reused in other datasets if necessary.\n<\/p><p>The last step consists in setting up proper permissions to share datasets. Read and Edition parameters can be set from the Permission tab. Also, specific Read and Edition parameters can be set for user groups.\n<\/p><p>The project is now completely loaded within Djeen and can be further edited and shared. Data can then be downloaded from Djeen. Individual samples can be downloaded from the \u201cFile\u201d tab while the whole dataset can be downloaded by performing a snapshot and downloading the resulting archive.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusion\">Conclusion<\/span><\/h2>\n<p>Djeen is a new Research Information Management System designed to answer laboratories' growing needs for flexibility in data management. It allows the sharing, secure storing and annotation of heterogeneous data types, streamlines repetitive annotations tasks and features import functions. Djeen organizes projects within a natural hierarchy similar to files and folders organization on disk. Templates (optionally used) allow automation and MI Information. These features were demonstrated in this report with the demonstration of a real use case for microarray data.\n<\/p><p>Djeen features a user-friendly installation procedure and web interface. It is conceived as a Joomla! component, has a fast learning curve and can be deployed over MySQL or PostgreSQL.\n<\/p><p>Future development include setting up an advanced interface for data requests, a scripting module to perform data processing directly from the UI, and an advanced authentication system using LDAP.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Availability_and_requirements\">Availability and requirements<\/span><\/h2>\n<p><b>Project name<\/b>: Database for Joomla!\u2019s Extensible Engine\n<\/p><p><b>Project home page<\/b>: <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/sourceforge.net\/projects\/djeen\" target=\"_blank\">https:\/\/sourceforge.net\/projects\/djeen<\/a>\n<\/p><p><b>Operating system(s)<\/b>: Platform independent\n<\/p><p><b>Programming language<\/b>: PHP\/Javascript\/SQL\/Perl\n<\/p><p><b>Other requirements<\/b>: A Linux server running Apache2\/Perl 5.x\/\/PHP 5.3+\/MySQL or PostgreSQL\n<\/p><p><b>License<\/b>: CeCILL\n<\/p><p><b>Any restrictions to use by non-academics<\/b>: Please contact directly the authors for additional information.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Abbreviations\">Abbreviations<\/span><\/h2>\n<p>CMS: Content Management System\n<\/p><p>EULA: End-user license Agreement\n<\/p><p>Djeen: Database for Joomla!\u2019s Extensible Engine\n<\/p><p>RIMS: Research Information Management System\n<\/p><p>MI: Minimum Information\n<\/p><p>MIAME: Minimum Information About A Microarray Experiment\n<\/p><p>UI: User Interface\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Declarations\">Declarations<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h3>\n<p>We would like to thank Dr Fran\u00e7oise Birg and Wahiba Gherraby for their valuable comments on the manuscript. We would also thank the Marseille proteomics core for their involvement.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Funding\">Funding<\/span><\/h3>\n<p>This project has been funded by an Institut National du Cancer\/Institut National de la sant\u00e9 et de la Recherche M\u00e9dicale grant to G.B. Additional support for Olivier Stahl was obtained from Aix-Marseille University and from the Cancerop\u00f4le Provence-Alpes-C\u00f4te d\u2019Azur. The Djeen server is funded by a Fondation pour la Recherche M\u00e9dicale grant to G.B. and currently maintained by the Datacentre for IT and Scientific Computing of CRCM. Support for Hugo Duvergey is given partly by the R\u00e9gion Languedoc-Roussillon (GEPETOS 2007 contract). OV is supported by the Centre National de la Recherche Scientifique.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Competing_interests\">Competing interests<\/span><\/h3>\n<p>Authors declare that they have no competing interests.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Authors.E2.80.99_contributions\">Authors\u2019 contributions<\/span><\/h3>\n<p>OS designed the database scheme, software architecture and implemented the web interface and database. He also wrote the manuscript. HD developed installation procedure, finalized code for release and wrote documentation. AG designed import\/export functions. FB and ADV contributed the UI (projects and file views). PF provided initial discussions in interface and microarray data management. SG and OV designed data and template models and provided helpful suggestions. GB funded the project, wrote documentation and finalized the manuscript. All authors participated to debug and release the 1.5 version. 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(2008). \"Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes\". <i>Clinical Cancer Research<\/i> <b>14<\/b> (16): 5158-65. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1158%2F1078-0432.CCR-07-4756\" target=\"_blank\">10.1158\/1078-0432.CCR-07-4756<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18698033\" target=\"_blank\">18698033<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Biological+processes+associated+with+breast+cancer+clinical+outcome+depend+on+the+molecular+subtypes&rft.jtitle=Clinical+Cancer+Research&rft.aulast=Desmedt%2C+C.%3B+Haibe-Kains%2C+B.%3B+Wirapati%2C+P.%3B+Buyse%2C+M.%3B+Larsimont%2C+D.%3B+Bontempi%2C+G.%3B+Delorenzi%2C+M.%3B+Piccart%2C+M.%3B+Sotiriou%2C+C.&rft.au=Desmedt%2C+C.%3B+Haibe-Kains%2C+B.%3B+Wirapati%2C+P.%3B+Buyse%2C+M.%3B+Larsimont%2C+D.%3B+Bontempi%2C+G.%3B+Delorenzi%2C+M.%3B+Piccart%2C+M.%3B+Sotiriou%2C+C.&rft.date=2008&rft.volume=14&rft.issue=16&rft.pages=5158-65&rft_id=info:doi\/10.1158%2F1078-0432.CCR-07-4756&rft_id=info:pmid\/18698033&rfr_id=info:sid\/en.wikipedia.org:Journal:Djeen_(Database_for_Joomla!%E2%80%99s_Extensible_Engine):_A_research_information_management_system_for_flexible_multi-technology_project_administration\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. In one case a direct reference to a citation number was changed to reference the author names instead.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192202\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.439 seconds\nReal time usage: 0.471 seconds\nPreprocessor visited node count: 14457\/1000000\nPreprocessor generated node count: 29290\/1000000\nPost\u2010expand include size: 127337\/2097152 bytes\nTemplate argument size: 41504\/2097152 bytes\nHighest expansion depth: 18\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 432.748 1 - -total\n 80.24% 347.231 1 - Template:Reflist\n 73.80% 319.374 16 - Template:Cite_journal\n 70.35% 304.451 16 - Template:Citation\/core\n 14.38% 62.249 1 - Template:Infobox_journal_article\n 13.79% 59.672 1 - Template:Infobox\n 11.17% 48.321 35 - Template:Citation\/identifier\n 8.30% 35.921 80 - Template:Infobox\/row\n 3.88% 16.773 75 - Template:Hide_in_print\n 3.68% 15.918 16 - Template:Citation\/make_link\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:7923-0!*!0!!en!5!* and timestamp 20181214192201 and revision id 23624\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Djeen_(Database_for_Joomla!%E2%80%99s_Extensible_Engine):_A_research_information_management_system_for_flexible_multi-technology_project_administration\">https:\/\/www.limswiki.org\/index.php\/Journal:Djeen_(Database_for_Joomla!%E2%80%99s_Extensible_Engine):_A_research_information_management_system_for_flexible_multi-technology_project_administration<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","8552328b588cc33465f115d2b29dced0_images":["https:\/\/www.limswiki.org\/images\/b\/b0\/Fig1_Stahl_BMCResearchNotes2013_6.jpg","https:\/\/www.limswiki.org\/images\/3\/38\/Fig2_Stahl_BMCResearchNotes2013_6.jpg","https:\/\/www.limswiki.org\/images\/b\/b4\/Fig3_Stahl_BMCResearchNotes2013_6.jpg","https:\/\/www.limswiki.org\/images\/8\/8f\/Fig4_Stahl_BMCResearchNotes2013_6.jpg"],"8552328b588cc33465f115d2b29dced0_timestamp":1544815321,"de90eb3652231af7bd081d7eedc00c72_type":"article","de90eb3652231af7bd081d7eedc00c72_title":"Design, implementation and operation of a multimodality research imaging informatics repository (Nguyen et al. 2015)","de90eb3652231af7bd081d7eedc00c72_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository","de90eb3652231af7bd081d7eedc00c72_plaintext":"\n\n\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\n\t\t\t\tJournal:Design, implementation and operation of a multimodality research imaging informatics repository\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\tFrom LIMSWiki\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tJump to: navigation, search\n\n\t\t\t\t\t\n\t\t\t\t\tFull article title\n \nDesign, implementation and operation of a multimodality research imaging informatics repositoryJournal\n \nHealth Information Science and SystemsAuthor(s)\n \nNguyen, Toan D.; Raniga, Parnesh; Barnes, David G.; Egan, Gary F.Author affiliation(s)\n \nMonash University, CSIROPrimary contact\n \nEmail: toan.nguyen@monash.eduYear published\n \n2015Volume and issue\n \n3 (Suppl 1)Page(s)\n \nS6DOI\n \n10.1186\/2047-2501-3-S1-S6ISSN\n \n2047-2501Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttp:\/\/www.hissjournal.com\/content\/3\/S1\/S6Download\n \nhttp:\/\/www.hissjournal.com\/content\/pdf\/2047-2501-3-S1-S6.pdf (PDF)\n\nContents\n\n1 Abstract \n2 Background \n3 Methods \n\n3.1 Requirements \n3.2 Informatics systems and data model \n3.3 Automatic data flows \n3.4 User interaction \n\n\n4 Results \n5 Discussion \n6 Conclusions \n7 Abbreviations \n8 Competing interests \n9 Declarations \n10 Authors' contributions \n11 Acknowledgements \n12 References \n13 Notes \n\n\n\nAbstract \nBackground: Biomedical imaging research increasingly involves acquiring, managing and processing large amounts of distributed imaging data. Integrated systems that combine data, meta-data and workflows are crucial for realising the opportunities presented by advances in imaging facilities.\nMethods: This paper describes the design, implementation and operation of a multi-modality research imaging data management system that manages imaging data obtained from biomedical imaging scanners operated at Monash Biomedical Imaging (MBI), Monash University in Melbourne, Australia. In addition to Digital Imaging and Communications in Medicine (DICOM) images, raw data and non-DICOM biomedical data can be archived and distributed by the system. Imaging data are annotated with meta-data according to a study-centric data model and, therefore, scientific users can find, download and process data easily.\nResults: The research imaging data management system ensures long-term usability, integrity inter-operability and integration of large imaging data. Research users can securely browse and download stored images and data, and upload processed data via subject-oriented informatics frameworks including the Distributed and Reflective Informatics System (DaRIS), and the Extensible Neuroimaging Archive Toolkit (XNAT).\n\nBackground \nModern clinical and biomedical research is increasingly reliant on imaging across a range of electromagnetic and acoustic wavelengths.[1][2][3] Contemporary studies now routinely collect images from more than one type of instrumentation - multi-modal studies[4] - and strive to obtain high spatial and\/or temporal resolution data. Multi-modal datasets provide complementary information[5] and enable sophisticated, multivariate analysis, while high-resolution datasets provide insight that was not possible only a few years ago. Extremely large multi-modal imaging studies can result in terabyte (TB) size data collections[6], although most research studies generate data in the megabyte (MB) to gigabyte (GB) range per subject. \nThe data volume per subject is multiplied by the increasing number of subjects per study. Many of today's high profile biomedical imaging studies have hundreds to thousands of participants.[7][8][9] Furthermore, many of these studies are longitudinal in nature and thus collect imaging data at multiple time points per subject. This multiplier effect results in a large collection of data that must be recorded per subject. Along with the imaging data, non-imaging and meta-data may also collected and should be stored and directly associated with the image data, especially if the data will be mined and\/or shared.[10]\nClinical informatics systems such as clinical picture archiving and communication systems (PACS) are commonplace[11], but their design, specifically for clinical settings, precludes effective use in a research environment. For example, the majority of PACS store data only in the Digital Imaging and Communications in Medicine (DICOM) format. The DICOM format consists of a binary header of tag\/value pairs. The tags (2 bytes) are keys but the descriptions of tags are stored independently in DICOM dictionaries and not in the data itself. The type of the value is contained in the tag\/value pair, which enables the accurate reading of the data and meta-data. Binary data is stored as a tag\/value pair. \nNeuroimaging processing and analysis is however typically conducted using a myriad of proprietary formats such as MINC[12], MRTrix image File (mif)[13] and Freesurfer File Format (mgh).[14] Recently, the Neuroimaging Informatics Technology Initiative (NIfTI) has provided a reference file format that is starting to become universally accepted and utilised.[15] The reason for the use of non-DICOM format was that traditionally, DICOM data for imaging modalities was stored as a single 2D image per file. For large 3D datasets, this means a lot of repetition of meta-data and slow reading of the data. The newer DICOM 3.0 format has alleviated some of these performance issues but at the expense of simplicity. Moreover the DICOM standards define a set of required meta-data based on the acquisition modality. Many of these required fields do not make sense for processed data and other relevant meta-data would need to be stored as DICOM tags which may not be understandable by all software. \nThe limitations of a solitary supported image format notwithstanding, it is not possible to keep track of and provide provenance for processed image or sensor data, which is usually in non-DICOM formats such as the NIfTI format. While some proprietary formats include support for meta-data by storing key value pairs, no such ability is present in NIfTI for example. Examples of such meta-data include the diffusion direction table that was used to acquire diffusion magnetic resonance imaging (MRI), control\/tag\/reference flags for arterial spin labelling images, various reference images and parameters for magnetic resonance (MR) spectroscopy data. Most of this meta-data is encoded as tag\/values in the DICOM header but is lost on conversion to other types. Other types of meta-data include descriptions of the type of data (e.g. brain gray matter segmentation) and of the tools and\/or pipelines that generated the data. Typically the later is done by utilising common naming conventions. However this can lead to ambiguity if all users and all tools do not implement the convention. Moreover, only a limited amount of information can be stored in this format.\nFurthermore the most commonly used DICOM data model is a subject (patient)-centric model. While the DICOM standard allows for a data model that is project-centric, such as the clinical trial information entity, but in practise, PACS usually do not support this feature. The patient or subject centric model in DICOM has been developed with the clinic in mind. Each subject\/patient is assumed to be independent of the other with little in common and it is not possible to group subjects together. Moreover the DICOM model does not inherently support the idea of longitudinal studies where the same patient is repeatedly scanned, some time interval apart. The ability to organise and quickly access data based on a project centric data model is essential to research applications which are project centric by nature. \nApart from the need for storing acquired data, research projects require the storage of post-processed data. The raw data is put through various automated and semi-automated algorithms to produce images and well as other data types and statistics. A description of all the processing steps and parameters needs to be stored with the data in order to keep track of how the final data was obtained. This provenance information is crucial in also keeping track of potential changes that may have occurred over different processing runs as well to search for data across projects that maybe similarly acquired and processed.\nThe need for raw data collection and management, as well the accurate recording of data provenance of processed data, for large biomedical imaging research studies, has resulted in the recent development of software packages, unlike clinical picture archiving and communication systems (PACS), that are designed specifically for research studies.[16][17][18][19] Along with the collection and storage of the primary data, these systems have been designed to store processed data as well as provenance information regarding the processing steps[20], although tight integration of the provenance information within the informatics platform is still under active research and development. Currently, in many such systems, provenance information is just another piece of meta-data that is optional. It's formatting and contents are up to the users. With tight integration, the province information would be required, would follow a known format and be ingestible by the system. The difficulty with this is that no universal standard for provenance in medical imaging exists either. Processed data storage and access is a critically important area since the size of processed datasets can be many tens of times larger than the original dataset, and in many cases are expensive to recompute.\nWhile informatics platforms for medical imaging are available, implementing an informatics strategy at a research-focused imaging facility is a challenging task. It depends on integrating acquisition systems (modalities) with good imaging informatics practise realised as a data model-based system, underpinned by archival-grade data storage infrastructure, and complete with functional and practical user interfaces. Most of the informatics platforms are oriented around the Project-Subject-Study-Data (PSSD) model but differ slightly in their implementation details and access methods. In this paper we describe the implementation of the informatics systems and data flows at the Monash Biomedical Imaging (MBI) facility at Monash University. Moreover we describe how we developed a set of tools and standard practises to that have enabled the efficient storage and access of biomedical imaging data. \n\nMethods \nRequirements \nWe start by considering a concise listing of the main requirements of an imaging informatics system at Monash Biomedical Imaging. A full requirements specification would be too long for this paper; instead, we focus on the core capabilities needed to support a generic multi-modal, multi-subject, longitudinal study - the core research activity we endeavour to enable and support.\n1) imaging data from DICOM capable modalities (e.g. MRI) must be, to a large extent, automatically routed from the point of acquisition to the imaging informatics system;\n2) imaging and non-imaging data from non-DICOM capable modalities (e.g. EEG) must be, to a large extent, easily manually uploaded to the imaging informatics system or uploaded using scripts and command line tools;\n3) imaging and non-imaging data and meta-data must be stored on secure, reliable, research grade backed-up storage;\n4) upon ingest of DICOM-format images, standard meta-data should, to a large extent, be automatically extracted (\"harvested\") from the DICOM files and recorded in the imaging informatics system;\n5) human imaging data must be accessible by standard radiology software for review by the MBI radiologist;\n6) imaging and non-imaging data must be organised in a study centric fashion, supporting multi-modal and longitudinal image collections per study subject;\n7) an end user tool should exist to aid users in defining the set of meta-data to associate with a study and its subjects, and in defining the data acquisition(s) that comprise the study;\n8) all data must be uniquely identifiable without the need for real subject names or identifying information other than date of birth and gender;\n9) imaging and non-imaging data and meta-data must be available via a secure web portal to the owner (research leader) and their delegate\/s;\n10) imaging and non-imaging data must be transferable from within the secure web portal to the accessing workstation (\"download\") or to Monash University's high performance computing facility MASSIVE (\"transfer\");\n11) users should be able to manually package and upload processed data and record provenance (e.g. link to the source data set\/s); and\n12) a command-line based tool must be available that enables search of the image informatics system, and upload and download of data collections, for use in batch processing workflows. \n\nInformatics systems and data model \nAt MBI we currently have two informatics platforms deployed, namely DaRIS[17] and XNAT.[16] DaRIS is a framework built on the top of Mediaflux (Architecta Pty Ltd, Melbourne, Australia), a commercial media asset management system, and is specifically designed for medical imaging data. Assets in Mediaflux are associated with XML meta-data that can be automatically extracted from data or input manually by users. Mediaflux provides a set of services for data management, such as finding, storing and retrieving assets, archiving and handling large data, and data analysis and transformation. To protect data, Mediaflux implements a strong authorisation model in which role based authorisation is used to access to data and each repository has independent access control. DaRIS builds on these capabilities by imposing a data model and a set of methods. \nThe data model adopted at MBI is the project-subject-study-data (PSSD) model that is used in DaRIS, and although the elements of the XNAT data model are named differently, they can be mapped directly to the PSSD data model (Figure 1). The PSSD data model is a hierarchical data model that is anchored at the project level, unlike the DICOM data model. Each object in the model has an independent citable identifier that allows the object to be referenced uniquely in a distributed environment, with the uniqueness property in DaRIS enforced by Mediaflux. A method declares what meta-data must and optionally can be entered when a new entity (project, subject, study or data set) is created. New methods can be created using Tool Command Language (TCL) script which Mediaflux natively supports, or Method Builder, which is a Mediaflux web interface plugin developed for us by the Victorian e-Research Strategic Initiative (VeRSI). \n\n\n\n\n\n\n\n\n\n Figure 1. The data models of DaRIS and XNAT = illustrate the one to one correspondence between two models. The data model diverges slightly at the Scan\/Data level in that XNAT has specific subclasses (Reconstruction and Image Assessment) for post-processed data deriving from Scan whereas this information is contained in the meta-data and methods in DaRIS. Study and experiment are the same concept.\n\n\n\nXNAT, a free Open Source Software imaging informatics platform, is designed for common management and productivity tasks for imaging and associated data. It has been developed based on a three tiered architecture including a data archive, a user interface and a middleware \"engine\". The XNAT data model is equivalent to the DaRIS one with project-subject-experiment-data forming the hierarchy. While XNAT does not have an explicit method type like DaRIS, extra data and meta-data can be entered into XNAT. Researchers can work with their data easily using the XNAT web interface to upload data using data entry forms, perform data-type-specific search, view detailed reports and experimental data and access research workflows. Like DaRIS, XNAT has an in-built DICOM server that can be programmed to archive incoming data based on values in specified DICOM tags. XNAT has an HTTP based REST API for querying, retrieving and storing data.\nThe XNAT and DaRIS data-models diverge slightly at the Scan\/Data level in that XNAT has specific subclasses (Reconstruction and Image Assessment) for post-processed data deriving from Scan whereas this information is contained in the meta-data and methods in DaRIS. For primary data, the data models are equivalent. For processed data, XNAT stores the data within reconstructions and image assessments (we only utilise the later) which is a subclass of scan. In DaRIS, no such distinction exists and the associated meta-data at the Data level reflects the difference between primary and processed data.\nIn order to simply the access to the systems, hide differences between data models and enforce some meta-data entry, we have developed python classes that map onto the PSSD model for interacting with DaRIS and XNAT. These classes hide the lower level interaction from the user and allow them to utilise both in a similar manner. Moreover, the python tools enforce the entry of certain meta-data. For example, provenance information needs to be attached to every processed dataset before it is uploaded. Similarly a description and version of the tools or workflow that produced the dataset needs to be entered.\nThe python tools are currently being utilised for automated workflows. These workflows are scripts\/programs that are designed to download appropriate datasets from projects, perform a task and uploaded processed data back onto the informatics system. An example of this is the Freesurfer recon_all workflow[14] that segments brain MRI images. Another example is the preprocessing of functional MRI data to correct for head-motion and distortion. \n\nAutomatic data flows \nThe automatic data flows in the MBI imaging informatics system are shown in Figure 2. Data sources (i.e. scanners) are shown on the left. The Syngo-via server is a clinical PACS system and radiological reporting tool (Siemens Via server, Siemens, Erlangan, Germany). The Monash petascale Large Research Data Storage (LaRDS) system provides the networked, high performance storage and backup system. DaRIS and XNAT are the front-end research informatics platforms described in the previous section that we currently use and support. \n\n\n\n\n\n\n\n\n\n Figure 2. The acquisition and automated data flows through the current system. Data from the scanners are pushed directly to DaRIS or to Syngo-via Server and then forwarded to XNAT or DaRIS.\n\n\n\nDICOM data from human subjects (control or otherwise) MRI scans are sent from the scanner to the Syngo-via server and reviewed by a radiologist for incidental and adverse findings. This data route currently is only used for our 3 Telsa Siemens Skyra MRI scanner (Siemens, Erlangan Germany) but future facilities acquiring imaging data from human volunteers will join into this path. From the Syngo-via server, data is forwarded to one or both research informatics platforms (DaRIS and XNAT currently, but others easily supported) based on the values in specified DICOM tags. All DICOM data arriving at the Syngo-via server are simply forwarded to a secondary DICOM server running on Mediaflux for \"last resort\" archiving. Whilst DaRIS is our principal (and default) repository for biomedical imaging data and meta-data, XNAT is available where it presents an advantage or preference for the users.\nIt should be noted that all subjects (human and non-human) are assigned unique identifiers (subject identifier and scan identifier) prior to scanning. Identifying and other associated meta-data for human subjects is stored in a separately maintained, secure, administrative database. For human subjects, no identifying data is stored in the DICOM images apart from gender and date of birth. If a subject must be identified (e.g. for reporting of incidental findings), it is done so via the mapping in the secure administrative database real identities.\nA normal clinical PACS operates only on DICOM images via DICOM communication. In a research imaging data management environment raw data (pre-image reconstruction) and non-DICOM image data must also be managed, since pre-clinical imaging scanners do not in general implement full DICOM support. Data from the 9.4T and microPET\/CT scanners are sent directly to the associated platforms e.g. DaRIS either automatically via export of DICOMS or semi-automatic uploads of proprietary formats using scripts. Raw data from the 3T Skyra scanner is also sent to a server and then archived to LaRDS on request from projects. This can then be reconstructed and post-processed with different algorithms to those available on the scanner.\nFor large datasets that are required to be accessed often, digital object identifiers (DOIs) and digital handles are being implemented in DaRIS as long-lived references to the datasets. \n\nUser interaction \nResearchers access data stored in DaRIS and XNAT using a web portal, client programs and scripts (Figure 3). Both DaRIS and XNAT implement strong security protocols with role based authenticated access to restrict unintended access. Layered on the permission model of Mediaflux, DaRIS provides four layers of role-based authorisation to protect data objects and services. Each project in DaRIS belongs to users with role-based access that determines their access to assets and services: (i) the nominated project administrator(s) can control access to the project and modify project team\/roles, (ii) subject administrator(s) can create and administer subjects, (iii) user(s) can access all research data but not subject identity (where that information has optionally been directly entered by the project or subject administrator - by default subject identity is not stored in DaRIS), and (iv) guest(s) can access meta-data only. \n\n\n\n\n\n\n\n\n\n Figure 3. User interaction. Illustration of the different ways the user can interact with the informatics system.\n\n\n\nDaRIS can operate in a distributed environment and projects can be stored and federated over multiple servers. Since the location of assets associated with data and meta-data is largely transparent to the users and accessible from anywhere through mechanisms including distributed queries, remote access and replication, imaging data stored on DaRIS can be accessed from researchers at different institutions using client programs, command line tools and web portals. As a result, DaRIS provides an efficient way to access data across and within large collaborations. Authenticated users can download data easily using the DaRIS web portal as shown in Figure 4. They can download imaging data of studies, subjects or even an entire project using \"shopping carts\", and transcoding to popular medical image formats can be applied prior to download. Users can also find and download their data with client scripts which provide a convenient way to process imaging data inside batch scripts or programs developed in their preferred programming languages. For example, users of the Multi-modal Australian ScienceS Imaging and Visualisation Environment (MASSIVE) (http:\/\/www.massive.org.au) high performance computing facility can access and process imaging data that is downloaded from DaRIS. \n\n\n\n\n\n\n\n\n\n Figure 4. User interface for DaRIS. The web based user interface of DaRIS showing the main interface panel in (a) and the \"cart\" functionality in (b).\n\n\n\nXNAT can control the access of an individual user down to the single record level by using a hybrid XML relational database structure. When a user retrieves data that are stored in the relational database, XNAT checks whether or not the user is permitted access to the data by using the security protocols defined in XML data model. The XML security protocol is defined by selecting one or more security fields that are assigned one or more allowed values in each user's account. XNAT project administrators can assign access rules for users of the project using administrative tools included in the XNAT web application. XNAT also provides a very flexible HTTP\/REST based API for access, control and upload of data. Due to the flexibility of this API and the ability to program XNAT in a language-independent manner, XNAT is a preferred platform for projects that perform significant sequences of automated steps in data management (including on ingest).\nNon-DICOM and processed data can be uploaded via the DaRIS and XNAT portals, and using scripts. For DaRIS, post-processed data is added at the same level in the hierarchy as the originating data, but is tagged as being post-processed and referenced to the original dataset. Processed data can originate from more than one data set, as would be the case for a cohort based atlas image in a multi-subject study. In XNAT, post-processed data are tagged as reconstructions or image assessments (subclass of scans). Reconstructions are post-processed raw data or image data that are not derivatives. Image assessments are derivative images or statistics. \n\nResults \nOur system, implemented over the period October 2011 to July 2012 and refined in the intervening time, successfully realises the core capability requirements outlined above. All human imaging projects presently being undertaken at MBI on the Skyra 3T scanner are using the MBI imaging informatics system - and specifically the DaRIS backend - for the management, archive and retrieval of MR images. Many non-human imaging projects, using e.g. the small-bore high-field MR scanner or the small-bore microCT\/PET instrument, are also using the system as it provides a simple and reliable image management platform. Additionally, several large projects are being carried out at Monash University using data acquired elsewhere but federated into the Monash University DaRIS system. Large cohort longitudinal studies commenced at MBI will use the imaging informatics system from the outset. Presently (June 2014) there are nearly 100 distinct research projects registered in the system, and 110 users. The total compressed size of ingested data exceeds 1 TB. While this may be considered a relatively small volume, the uncompressed data size is 3-5 times this number. We expect significant growth as large imaging studies get underway and processed data and provenace information are archived together with the raw acquired datasets.\n\nDiscussion \nBiomedical imaging studies, especially multi-modal, longitudinal studies of large subject cohorts, generate large collections of data that need to be stored, archived and accessed. Contemporary mid-range MRI based studies can easily accumulate terabytes of data annually. The appropriate use of meta-data, and the recording of provenance for processed data collections, is critical in enabling integrative science, as well as establishing the long term quality and value of the data. The integration of image informatics platforms with the scientific instrumentation, with research quality archival data stores, and with performant processing systems (e.g. compute clusters) is critical in meeting the challenge of extracting new knowledge from biomedical imaging research data.\nThe system implemented at MBI and described in this article, caters for the needs of a large research imaging centre that generates data from human and non-human imaging experiments. The data is made available to researchers using two informatics platforms, namely DaRIS and XNAT. DaRIS is a project that, while ready for use, is undergoing active development and addition of features. Our close relationship with the DaRIS developers allows us to explore and modify the behaviour of the system to suit, and to provide input on future development directions. Our choice to support XNAT as well is driven by user demand, but effectively positions us to undertake a direct evaluation of the relative strengths, weaknesses, and future opportunities for both systems. In particular, we are very interested in developing interoperability between DaRIS and XNAT to allow flexibility in choice of tool for accessing and manipulating archival image and meta-data. We are also developing a file system based informatics platform based on the python classes. This will give users the ability to either cache their data or to use the python tools and workflows using data from a local filesystem. \nCurrently, the DaRIS platform is being developed to natively support additional data formats, both standardised and vendor specific formats. This work will enable the automated extraction of relevant meta-data from the supported formats, and the display of image \"thumbnails\" in the web interface. Another avenue of development is focused on workflows for processing data. Workflows can be programmed in XNAT already but are restricted to run on the XNAT host. Moreover, the pipeline descriptions are programmed using an XML type language specific to XNAT. To alleviate these issues, workflows in DaRIS are currently being developed using the established and well known workflow engines NIMROD[21] and KEPLER[22] and will be designed to distribute computational workload across HPC systems such as MASSIVE and the NeCTAR (http:\/\/www.nectar.org.au) Research Cloud. The automatic provenance tracking already available in Kepler brings a significant advantage presently lacking in XNAT workflows. \nWithin the context of workflows, we are exploring the choice of \"push\" versus \"pull\" processing. The work described above is focussed on push workflows, where (usually implicit) actions within the informatics system initiate processing of data: the data is pushed out to a processing system, the data are processed, and the results ingested. This is appropriate for wholly automated processing of large, rigidly self consistent data sets (i.e. many images that are acquired identically and need to be processed identically), with high throughput. However, for smaller bespoke projects, the pull style of workflow may be more suitable, and in particular enables mostly automated workflows but with manual intervention and inspection. To many users the pull workflow is more natural and controllable. The python tools that have been developed are utilised to develop \"pull\" type workflows that can be run independently of the informatics system and not tied to any computation platform. For example we have started providing nipype workflows tailored for acquisitions on our scanner for typical neuroimaging tasks. Nipype is workflow\/pipeline engine written in python specifically for the medical imaging\/neuroimaging community.[23] These workflows are paired with the python tools to download appropriate datasets from projects, perform the task and uploaded processed data back onto the informatics system. An example of this is the Freesurfer recon_all workflow[14] that segments brain MRI images. Another example is the preprocessing of functional MRI data to correct for head-motion and distortion. The advantage of the pull type of workflows is that they are distributed and not confined to the hardware of the informatics system. These allow them to be run from any computer supporting the tools used in the workflow with a cost of data transfer to and from the informatics system. \n\nConclusions \nA research imaging data management system based on DaRIS and XNAT has been designed and implemented to enable researchers to acquire, manage and analyse large, longitudinal biomedical imaging datasets. The system provides stable long-term storage data and sophisticated support tools for multi-modality biomedical imaging research. Current developments of DaRIS include enhancements to integrate scientific and computational push and pull workflows with the managed data repository. In future work, imaging data will be integrated with the Australian National Data Service (ANDS) registry to make better use of data outputs, and biomedical atlases to provide more quantitative information.\n\nAbbreviations \nAPI: application programming interface \nCT: computer tomography\nDaRIS: distributed and reflective informatics system\nDICOM: digital imaging and communications in medicine\nDOI: digital object identifier\nEEG: Electroencephalography\nGB: gigabyte\nHTTP: hypertext transfer protocol\nHPC: high performance computing\nLaRDS: large research data storage\nMB: megabyte\nMBI: Monash Biomedical Imaging\nMRI: magnetic resonance imaging\nNiFTI: neuroimaging informatics technology initiative\nPACS: picture archiving and communication system\nPSSD: project-subject-study-data\nRAID: redundant array of independent disks\nTB: terabyte\nTCL: tool command language\nVeRSI: Victorian e-research strategic initiative\nXML: extensible markup language\nXNAT: extensible neuroimaging archive toolkit\n\nCompeting interests \nThe authors declare that they have no competing interests.\n\nDeclarations \nThe authors would like to thank the Monash Biomedical Imaging, Monash University, Melbourne, Australia for financial support.\n\nAuthors' contributions \nGFE, DGB and PR developed the background, designed the method and analysed the results. TDN, PR and DGB implemented the methods and provided figures and data. GFE was the leader of this work. All authors read and approved the final manuscript.\n\nAcknowledgements \nWe thank N. Killeen and W. Liu (University of Melbourne) and J. Lohrey (Arcitecta) for developing and supporting the DaRIS code and web portal. We thank N. McPhee and S. Dart (Monash University) for local support of DaRIS and the Monash LaRDS infrastructure and we thank R. Keil and C. Chow for early designs of the MBI data flow. The DaRIS Method Builder was developed by A. Glenn, S. Izzo, R. Rothwell and S. Bennett (VeRSI). We thank W. Goscinski and P. McIntosh (Monash University) and C. West (VPAC) for supporting interoperation of DaRIS with the MASSIVE facility. T. D. Nguyen acknowledges support from the National Imaging Facility. The VLSCI's Life Sciences Computation Centre is a collaboration between Melbourne, Monash and La Trobe Universities and an initiative of the Victorian Government, Australia. The authors would like to thank the Monash Biomedical Imaging, Monash University, Melbourne, Australia for financial support.\nThis article has been published as part of Health Information Science and Systems Volume 3 Supplement 1, 2015: Proceedings of the Health Informatics Society of Australia Big Data Conference (HISA 2013). The full contents of the supplement are available online at http:\/\/www.hissjournal.com\/supplements\/3\/S1\/.\n\nReferences \n\n\n\u2191 Lauterbur, P.C. (1973). \"Image Formation by Induced Local Interactions: Examples Employing Nuclear Magnetic Resonance\". Nature 242 (5394): 190-1. doi:10.1038\/242190a0.   \n\n\u2191 Wang, X.; Pang, Y.; Ku, G.; Xie, X.; Stoica, G.; Wang, L.V. (2003). \"Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain\". Nature Biotechnology 21 (7): 803-6. doi:10.1038\/nbt839. PMID 12808463.   \n\n\u2191 Ledley, R.S.; Di Chiro, G.; Luessenhop, A.J.; Twigg, H.L. 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NeuroImage 42 (1): 178-95. doi:10.1016\/j.neuroimage.2008.04.186. PMC PMC2664747. PMID 18519166. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2664747 .   \n\n\u2191 Abramson, D.; Bethwaite, B.; Enticott, C.; Garic, S.; Peachey, T. (2011). \"Parameter Exploration in Science and Engineering Using Many-Task Computing\". IEEE Transactions on Parallel and Distributed Systems 22 (6): 960-973. doi:10.1109\/TPDS.2010.177.   \n\n\u2191 Lud\u00e4scher, B.; Altintas, I.; Berkley, C. et al. (2006). \"Scientific workflow management and the Kepler system. Special issue: workflow in grid systems\". Concurrency and Computation: Practice & Experience 18 (10): 1039-1065. doi:10.1002\/cpe.v18:10.   \n\n\u2191 Gorgolewski, K.; Burns, C.D.; Madison, C. et al. (2011). \"Nipype: a flexible, lightweight and extensible neuroimaging data processing framework in python\". Frontiers in Neuroinformatics 5: 13. doi:10.3389\/fninf.2011.00013. PMC PMC3159964. PMID 21897815. http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3159964 .   \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.\n\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\">https:\/\/www.limswiki.org\/index.php\/Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository<\/a>\n\t\t\t\t\tCategories: LIMSwiki journal articles (added in 2016)LIMSwiki journal articles (all)LIMSwiki journal articles on bioinformaticsLIMSwiki journal articles on imaging informatics\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\n\t\t\n\t\t\tNavigation menu\n\t\t\t\t\t\n\t\t\tViews\n\n\t\t\t\n\t\t\t\t\n\t\t\t\tJournal\n\t\t\t\tDiscussion\n\t\t\t\tView source\n\t\t\t\tHistory\n\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\t\n\t\t\t\tPersonal tools\n\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\tLog in\n\t\t\t\t\t\t\t\t\t\t\t\t\tRequest account\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\n\t\t\t\t\n\t\t\t\n\t\t\t\t\n\t\tNavigation\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tMain page\n\t\t\t\t\t\t\t\t\t\t\tRecent changes\n\t\t\t\t\t\t\t\t\t\t\tRandom page\n\t\t\t\t\t\t\t\t\t\t\tHelp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tSearch\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t \n\t\t\t\t\t\t\n\t\t\t\t\n\n\t\t\t\t\t\t\t\n\t\t\n\t\t\t\n\t\t\tTools\n\n\t\t\t\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tWhat links here\n\t\t\t\t\t\t\t\t\t\t\tRelated changes\n\t\t\t\t\t\t\t\t\t\t\tSpecial pages\n\t\t\t\t\t\t\t\t\t\t\tPermanent link\n\t\t\t\t\t\t\t\t\t\t\tPage information\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\tPrint\/export\n\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tCreate a book\n\t\t\t\t\t\t\t\t\t\t\tDownload as PDF\n\t\t\t\t\t\t\t\t\t\t\tDownload as Plain text\n\t\t\t\t\t\t\t\t\t\t\tPrintable version\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\n\t\t\n\t\tSponsors\n\t\t\n\t\t\t \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n \r\n\n\t\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\n\t\t\n\t\t\n\t\t\t\n\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t This page was last modified on 12 January 2016, at 20:22.\n\t\t\t\t\t\t\t\t\tThis page has been accessed 1,276 times.\n\t\t\t\t\t\t\t\t\tContent is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.\n\t\t\t\t\t\t\t\t\tPrivacy policy\n\t\t\t\t\t\t\t\t\tAbout LIMSWiki\n\t\t\t\t\t\t\t\t\tDisclaimers\n\t\t\t\t\t\t\t\n\t\t\n\t\t\n\t\t\n\n","de90eb3652231af7bd081d7eedc00c72_html":"<body class=\"mediawiki ltr sitedir-ltr ns-206 ns-subject page-Journal_Design_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository skin-monobook action-view\">\n<div id=\"rdp-ebb-globalWrapper\">\n\t\t<div id=\"rdp-ebb-column-content\">\n\t\t\t<div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\">\n\t\t\t\t<a id=\"rdp-ebb-top\"><\/a>\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Design, implementation and operation of a multimodality research imaging informatics repository<\/h1>\n\t\t\t\t\n\t\t\t\t<div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\">\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\n\t\t\t\t\t<!-- start content -->\n\t\t\t\t\t<div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p><b>Background:<\/b> Biomedical imaging research increasingly involves acquiring, managing and processing large amounts of distributed imaging data. Integrated systems that combine data, meta-data and workflows are crucial for realising the opportunities presented by advances in imaging facilities.\n<\/p><p><b>Methods:<\/b> This paper describes the design, implementation and operation of a multi-modality research imaging data management system that manages imaging data obtained from biomedical imaging scanners operated at Monash Biomedical Imaging (MBI), Monash University in Melbourne, Australia. In addition to <a href=\"https:\/\/www.limswiki.org\/index.php\/DICOM\" title=\"DICOM\" target=\"_blank\" class=\"wiki-link\" data-key=\"f0c7c747895286ff8785b6ed4dbc7ec0\">Digital Imaging and Communications in Medicine<\/a> (DICOM) images, raw data and non-DICOM biomedical data can be archived and distributed by the system. Imaging data are annotated with meta-data according to a study-centric data model and, therefore, scientific users can find, download and process data easily.\n<\/p><p><b>Results:<\/b> The research imaging data management system ensures long-term usability, integrity inter-operability and integration of large imaging data. Research users can securely browse and download stored images and data, and upload processed data via subject-oriented <a href=\"https:\/\/www.limswiki.org\/index.php\/Informatics\" title=\"Informatics\" class=\"mw-disambig wiki-link\" target=\"_blank\" data-key=\"ea0ff624ac3a644c35d2b51d39047bdf\">informatics<\/a> frameworks including the Distributed and Reflective Informatics System (DaRIS), and the Extensible Neuroimaging Archive Toolkit (XNAT).\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Background\">Background<\/span><\/h2>\n<p>Modern clinical and biomedical research is increasingly reliant on imaging across a range of electromagnetic and acoustic wavelengths.<sup id=\"rdp-ebb-cite_ref-LauterburImage73_1-0\" class=\"reference\"><a href=\"#cite_note-LauterburImage73-1\" rel=\"external_link\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-WangNon03_2-0\" class=\"reference\"><a href=\"#cite_note-WangNon03-2\" rel=\"external_link\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-LedleyComp74_3-0\" class=\"reference\"><a href=\"#cite_note-LedleyComp74-3\" rel=\"external_link\">[3]<\/a><\/sup> Contemporary studies now routinely collect images from more than one type of instrumentation - multi-modal studies<sup id=\"rdp-ebb-cite_ref-PichlerPET10_4-0\" class=\"reference\"><a href=\"#cite_note-PichlerPET10-4\" rel=\"external_link\">[4]<\/a><\/sup> - and strive to obtain high spatial and\/or temporal resolution data. Multi-modal datasets provide complementary <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" target=\"_blank\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a><sup id=\"rdp-ebb-cite_ref-CherryMulti09_5-0\" class=\"reference\"><a href=\"#cite_note-CherryMulti09-5\" rel=\"external_link\">[5]<\/a><\/sup> and enable sophisticated, multivariate analysis, while high-resolution datasets provide insight that was not possible only a few years ago. Extremely large multi-modal imaging studies can result in terabyte (TB) size data collections<sup id=\"rdp-ebb-cite_ref-AmuntsBig13_6-0\" class=\"reference\"><a href=\"#cite_note-AmuntsBig13-6\" rel=\"external_link\">[6]<\/a><\/sup>, although most research studies generate data in the megabyte (MB) to gigabyte (GB) range per subject. \n<\/p><p>The data volume per subject is multiplied by the increasing number of subjects per study. Many of today's high profile biomedical imaging studies have hundreds to thousands of participants.<sup id=\"rdp-ebb-cite_ref-EllisTheAus09_7-0\" class=\"reference\"><a href=\"#cite_note-EllisTheAus09-7\" rel=\"external_link\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-MuellerWays05_8-0\" class=\"reference\"><a href=\"#cite_note-MuellerWays05-8\" rel=\"external_link\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-HofmanTheRott09_9-0\" class=\"reference\"><a href=\"#cite_note-HofmanTheRott09-9\" rel=\"external_link\">[9]<\/a><\/sup> Furthermore, many of these studies are longitudinal in nature and thus collect imaging data at multiple time points per subject. This multiplier effect results in a large collection of data that must be recorded per subject. Along with the imaging data, non-imaging and meta-data may also collected and should be stored and directly associated with the image data, especially if the data will be mined and\/or shared.<sup id=\"rdp-ebb-cite_ref-LinkertMeta10_10-0\" class=\"reference\"><a href=\"#cite_note-LinkertMeta10-10\" rel=\"external_link\">[10]<\/a><\/sup>\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/Clinical_informatics\" title=\"Clinical informatics\" class=\"mw-redirect wiki-link\" target=\"_blank\" data-key=\"bda8123083aecb94afe79afec9ae4686\">Clinical informatics<\/a> systems such as clinical <a href=\"https:\/\/www.limswiki.org\/index.php\/Picture_archiving_and_communication_system\" title=\"Picture archiving and communication system\" target=\"_blank\" class=\"wiki-link\" data-key=\"523b73ff51fa83663dc0b1d59e6d0f05\">picture archiving and communication systems<\/a> (PACS) are commonplace<sup id=\"rdp-ebb-cite_ref-BryanTheBen99_11-0\" class=\"reference\"><a href=\"#cite_note-BryanTheBen99-11\" rel=\"external_link\">[11]<\/a><\/sup>, but their design, specifically for clinical settings, precludes effective use in a research environment. For example, the majority of PACS store data only in the Digital Imaging and Communications in Medicine (DICOM) format. The DICOM format consists of a binary header of tag\/value pairs. The tags (2 bytes) are keys but the descriptions of tags are stored independently in DICOM dictionaries and not in the data itself. The type of the value is contained in the tag\/value pair, which enables the accurate reading of the data and meta-data. Binary data is stored as a tag\/value pair. \n<\/p><p>Neuroimaging processing and analysis is however typically conducted using a myriad of proprietary formats such as MINC<sup id=\"rdp-ebb-cite_ref-BIC_MINC_12-0\" class=\"reference\"><a href=\"#cite_note-BIC_MINC-12\" rel=\"external_link\">[12]<\/a><\/sup>, MRTrix image File (mif)<sup id=\"rdp-ebb-cite_ref-TournierMRtrix12_13-0\" class=\"reference\"><a href=\"#cite_note-TournierMRtrix12-13\" rel=\"external_link\">[13]<\/a><\/sup> and Freesurfer File Format (mgh).<sup id=\"rdp-ebb-cite_ref-HarvardFreeSurfer_14-0\" class=\"reference\"><a href=\"#cite_note-HarvardFreeSurfer-14\" rel=\"external_link\">[14]<\/a><\/sup> Recently, the Neuroimaging Informatics Technology Initiative (NIfTI) has provided a reference file format that is starting to become universally accepted and utilised.<sup id=\"rdp-ebb-cite_ref-DFWG_NIfTI_15-0\" class=\"reference\"><a href=\"#cite_note-DFWG_NIfTI-15\" rel=\"external_link\">[15]<\/a><\/sup> The reason for the use of non-DICOM format was that traditionally, DICOM data for imaging modalities was stored as a single 2D image per file. For large 3D datasets, this means a lot of repetition of meta-data and slow reading of the data. The newer DICOM 3.0 format has alleviated some of these performance issues but at the expense of simplicity. Moreover the DICOM standards define a set of required meta-data based on the acquisition modality. Many of these required fields do not make sense for processed data and other relevant meta-data would need to be stored as DICOM tags which may not be understandable by all software. \n<\/p><p>The limitations of a solitary supported image format notwithstanding, it is not possible to keep track of and provide provenance for processed image or sensor data, which is usually in non-DICOM formats such as the NIfTI format. While some proprietary formats include support for meta-data by storing key value pairs, no such ability is present in NIfTI for example. Examples of such meta-data include the diffusion direction table that was used to acquire diffusion magnetic resonance imaging (MRI), control\/tag\/reference flags for arterial spin labelling images, various reference images and parameters for magnetic resonance (MR) spectroscopy data. Most of this meta-data is encoded as tag\/values in the DICOM header but is lost on conversion to other types. Other types of meta-data include descriptions of the type of data (e.g. brain gray matter segmentation) and of the tools and\/or pipelines that generated the data. Typically the later is done by utilising common naming conventions. However this can lead to ambiguity if all users and all tools do not implement the convention. Moreover, only a limited amount of information can be stored in this format.\n<\/p><p>Furthermore the most commonly used DICOM data model is a subject (patient)-centric model. While the DICOM standard allows for a data model that is project-centric, such as the clinical trial information entity, but in practise, PACS usually do not support this feature. The patient or subject centric model in DICOM has been developed with the clinic in mind. Each subject\/patient is assumed to be independent of the other with little in common and it is not possible to group subjects together. Moreover the DICOM model does not inherently support the idea of longitudinal studies where the same patient is repeatedly scanned, some time interval apart. The ability to organise and quickly access data based on a project centric data model is essential to research applications which are project centric by nature. \n<\/p><p>Apart from the need for storing acquired data, research projects require the storage of post-processed data. The raw data is put through various automated and semi-automated algorithms to produce images and well as other data types and statistics. A description of all the processing steps and parameters needs to be stored with the data in order to keep track of how the final data was obtained. This provenance information is crucial in also keeping track of potential changes that may have occurred over different processing runs as well to search for data across projects that maybe similarly acquired and processed.\n<\/p><p>The need for raw data collection and management, as well the accurate recording of data provenance of processed data, for large biomedical imaging research studies, has resulted in the recent development of software packages, unlike clinical picture archiving and communication systems (PACS), that are designed specifically for research studies.<sup id=\"rdp-ebb-cite_ref-MarcusTheExt07_16-0\" class=\"reference\"><a href=\"#cite_note-MarcusTheExt07-16\" rel=\"external_link\">[16]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-LohreyAnInt09_17-0\" class=\"reference\"><a href=\"#cite_note-LohreyAnInt09-17\" rel=\"external_link\">[17]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-BookNeuro13_18-0\" class=\"reference\"><a href=\"#cite_note-BookNeuro13-18\" rel=\"external_link\">[18]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-VanHornIsIt09_19-0\" class=\"reference\"><a href=\"#cite_note-VanHornIsIt09-19\" rel=\"external_link\">[19]<\/a><\/sup> Along with the collection and storage of the primary data, these systems have been designed to store processed data as well as provenance information regarding the processing steps<sup id=\"rdp-ebb-cite_ref-MacKenzieProv08_20-0\" class=\"reference\"><a href=\"#cite_note-MacKenzieProv08-20\" rel=\"external_link\">[20]<\/a><\/sup>, although tight integration of the provenance information within the informatics platform is still under active research and development. Currently, in many such systems, provenance information is just another piece of meta-data that is optional. It's formatting and contents are up to the users. With tight integration, the province information would be required, would follow a known format and be ingestible by the system. The difficulty with this is that no universal standard for provenance in medical imaging exists either. Processed data storage and access is a critically important area since the size of processed datasets can be many tens of times larger than the original dataset, and in many cases are expensive to recompute.\n<\/p><p>While informatics platforms for medical imaging are available, implementing an informatics strategy at a research-focused imaging facility is a challenging task. It depends on integrating acquisition systems (modalities) with good <a href=\"https:\/\/www.limswiki.org\/index.php\/Imaging_informatics\" title=\"Imaging informatics\" target=\"_blank\" class=\"wiki-link\" data-key=\"fc0ae6a154d8896767defefdb6d14d0e\">imaging informatics<\/a> practise realised as a data model-based system, underpinned by archival-grade data storage infrastructure, and complete with functional and practical user interfaces. Most of the informatics platforms are oriented around the Project-Subject-Study-Data (PSSD) model but differ slightly in their implementation details and access methods. In this paper we describe the implementation of the informatics systems and data flows at the Monash Biomedical Imaging (MBI) facility at Monash University. Moreover we describe how we developed a set of tools and standard practises to that have enabled the efficient storage and access of biomedical imaging data. \n<\/p>\n<h2><span class=\"mw-headline\" id=\"Methods\">Methods<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Requirements\">Requirements<\/span><\/h3>\n<p>We start by considering a concise listing of the main requirements of an imaging informatics system at Monash Biomedical Imaging. A full requirements specification would be too long for this paper; instead, we focus on the core capabilities needed to support a generic multi-modal, multi-subject, longitudinal study - the core research activity we endeavour to enable and support.\n<\/p><p>1) imaging data from DICOM capable modalities (e.g. MRI) must be, to a large extent, automatically routed from the point of acquisition to the imaging informatics system;\n<\/p><p>2) imaging and non-imaging data from non-DICOM capable modalities (e.g. EEG) must be, to a large extent, easily manually uploaded to the imaging informatics system or uploaded using scripts and command line tools;\n<\/p><p>3) imaging and non-imaging data and meta-data must be stored on secure, reliable, research grade backed-up storage;\n<\/p><p>4) upon ingest of DICOM-format images, standard meta-data should, to a large extent, be automatically extracted (\"harvested\") from the DICOM files and recorded in the imaging informatics system;\n<\/p><p>5) human imaging data must be accessible by standard radiology software for review by the MBI radiologist;\n<\/p><p>6) imaging and non-imaging data must be organised in a study centric fashion, supporting multi-modal and longitudinal image collections per study subject;\n<\/p><p>7) an end user tool should exist to aid users in defining the set of meta-data to associate with a study and its subjects, and in defining the data acquisition(s) that comprise the study;\n<\/p><p>8) all data must be uniquely identifiable without the need for real subject names or identifying information other than date of birth and gender;\n<\/p><p>9) imaging and non-imaging data and meta-data must be available via a secure web portal to the owner (research leader) and their delegate\/s;\n<\/p><p>10) imaging and non-imaging data must be transferable from within the secure web portal to the accessing workstation (\"download\") or to Monash University's high performance computing facility MASSIVE (\"transfer\");\n<\/p><p>11) users should be able to manually package and upload processed data and record provenance (e.g. link to the source data set\/s); and\n<\/p><p>12) a command-line based tool must be available that enables search of the image informatics system, and upload and download of data collections, for use in batch processing workflows. \n<\/p>\n<h3><span class=\"mw-headline\" id=\"Informatics_systems_and_data_model\">Informatics systems and data model<\/span><\/h3>\n<p>At MBI we currently have two informatics platforms deployed, namely DaRIS<sup id=\"rdp-ebb-cite_ref-LohreyAnInt09_17-1\" class=\"reference\"><a href=\"#cite_note-LohreyAnInt09-17\" rel=\"external_link\">[17]<\/a><\/sup> and XNAT.<sup id=\"rdp-ebb-cite_ref-MarcusTheExt07_16-1\" class=\"reference\"><a href=\"#cite_note-MarcusTheExt07-16\" rel=\"external_link\">[16]<\/a><\/sup> DaRIS is a framework built on the top of Mediaflux (Architecta Pty Ltd, Melbourne, Australia), a commercial media asset management system, and is specifically designed for medical imaging data. Assets in Mediaflux are associated with XML meta-data that can be automatically extracted from data or input manually by users. Mediaflux provides a set of services for data management, such as finding, storing and retrieving assets, archiving and handling large data, and data analysis and transformation. To protect data, Mediaflux implements a strong authorisation model in which role based authorisation is used to access to data and each repository has independent access control. DaRIS builds on these capabilities by imposing a data model and a set of methods. \n<\/p><p>The data model adopted at MBI is the project-subject-study-data (PSSD) model that is used in DaRIS, and although the elements of the XNAT data model are named differently, they can be mapped directly to the PSSD data model (Figure 1). The PSSD data model is a hierarchical data model that is anchored at the project level, unlike the DICOM data model. Each object in the model has an independent citable identifier that allows the object to be referenced uniquely in a distributed environment, with the uniqueness property in DaRIS enforced by Mediaflux. A method declares what meta-data must and optionally can be entered when a new entity (project, subject, study or data set) is created. New methods can be created using Tool Command Language (TCL) script which Mediaflux natively supports, or Method Builder, which is a Mediaflux web interface plugin developed for us by the Victorian e-Research Strategic Initiative (VeRSI). \n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"69f23cd65d50fc449ba970cf47c0b485\"><img alt=\"Fig1 Nguyen HealthInfoSciSys2015 3-Suppl1.jpg\" src=\"https:\/\/www.limswiki.org\/images\/6\/64\/Fig1_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 1. The data models of DaRIS and XNAT = illustrate the one to one correspondence between two models.<\/b> The data model diverges slightly at the Scan\/Data level in that XNAT has specific subclasses (Reconstruction and Image Assessment) for post-processed data deriving from Scan whereas this information is contained in the meta-data and methods in DaRIS. Study and experiment are the same concept.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>XNAT, a free Open Source Software imaging informatics platform, is designed for common management and productivity tasks for imaging and associated data. It has been developed based on a three tiered architecture including a data archive, a user interface and a middleware \"engine\". The XNAT data model is equivalent to the DaRIS one with project-subject-experiment-data forming the hierarchy. While XNAT does not have an explicit method type like DaRIS, extra data and meta-data can be entered into XNAT. Researchers can work with their data easily using the XNAT web interface to upload data using data entry forms, perform data-type-specific search, view detailed reports and experimental data and access research workflows. Like DaRIS, XNAT has an in-built DICOM server that can be programmed to archive incoming data based on values in specified DICOM tags. XNAT has an HTTP based REST API for querying, retrieving and storing data.\n<\/p><p>The XNAT and DaRIS data-models diverge slightly at the Scan\/Data level in that XNAT has specific subclasses (Reconstruction and Image Assessment) for post-processed data deriving from Scan whereas this information is contained in the meta-data and methods in DaRIS. For primary data, the data models are equivalent. For processed data, XNAT stores the data within reconstructions and image assessments (we only utilise the later) which is a subclass of scan. In DaRIS, no such distinction exists and the associated meta-data at the Data level reflects the difference between primary and processed data.\n<\/p><p>In order to simply the access to the systems, hide differences between data models and enforce some meta-data entry, we have developed python classes that map onto the PSSD model for interacting with DaRIS and XNAT. These classes hide the lower level interaction from the user and allow them to utilise both in a similar manner. Moreover, the python tools enforce the entry of certain meta-data. For example, provenance information needs to be attached to every processed dataset before it is uploaded. Similarly a description and version of the tools or workflow that produced the dataset needs to be entered.\n<\/p><p>The python tools are currently being utilised for automated workflows. These workflows are scripts\/programs that are designed to download appropriate datasets from projects, perform a task and uploaded processed data back onto the informatics system. An example of this is the Freesurfer recon_all workflow<sup id=\"rdp-ebb-cite_ref-HarvardFreeSurfer_14-1\" class=\"reference\"><a href=\"#cite_note-HarvardFreeSurfer-14\" rel=\"external_link\">[14]<\/a><\/sup> that segments brain MRI images. Another example is the preprocessing of functional MRI data to correct for head-motion and distortion. \n<\/p>\n<h3><span class=\"mw-headline\" id=\"Automatic_data_flows\">Automatic data flows<\/span><\/h3>\n<p>The automatic data flows in the MBI imaging informatics system are shown in Figure 2. Data sources (i.e. scanners) are shown on the left. The Syngo-via server is a clinical PACS system and radiological reporting tool (Siemens Via server, Siemens, Erlangan, Germany). The Monash petascale Large Research Data Storage (LaRDS) system provides the networked, high performance storage and backup system. DaRIS and XNAT are the front-end research informatics platforms described in the previous section that we currently use and support. \n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"dc9da8b64d9876b93f7c88801123b6fc\"><img alt=\"Fig2 Nguyen HealthInfoSciSys2015 3-Suppl1.jpg\" src=\"https:\/\/www.limswiki.org\/images\/5\/5e\/Fig2_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 2. The acquisition and automated data flows through the current system.<\/b> Data from the scanners are pushed directly to DaRIS or to Syngo-via Server and then forwarded to XNAT or DaRIS.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>DICOM data from human subjects (control or otherwise) MRI scans are sent from the scanner to the Syngo-via server and reviewed by a radiologist for incidental and adverse findings. This data route currently is only used for our 3 Telsa Siemens Skyra MRI scanner (Siemens, Erlangan Germany) but future facilities acquiring imaging data from human volunteers will join into this path. From the Syngo-via server, data is forwarded to one or both research informatics platforms (DaRIS and XNAT currently, but others easily supported) based on the values in specified DICOM tags. All DICOM data arriving at the Syngo-via server are simply forwarded to a secondary DICOM server running on Mediaflux for \"last resort\" archiving. Whilst DaRIS is our principal (and default) repository for biomedical imaging data and meta-data, XNAT is available where it presents an advantage or preference for the users.\n<\/p><p>It should be noted that all subjects (human and non-human) are assigned unique identifiers (subject identifier and scan identifier) prior to scanning. Identifying and other associated meta-data for human subjects is stored in a separately maintained, secure, administrative database. For human subjects, no identifying data is stored in the DICOM images apart from gender and date of birth. If a subject must be identified (e.g. for reporting of incidental findings), it is done so via the mapping in the secure administrative database real identities.\n<\/p><p>A normal clinical PACS operates only on DICOM images via DICOM communication. In a research imaging data management environment raw data (pre-image reconstruction) and non-DICOM image data must also be managed, since pre-clinical imaging scanners do not in general implement full DICOM support. Data from the 9.4T and microPET\/CT scanners are sent directly to the associated platforms e.g. DaRIS either automatically via export of DICOMS or semi-automatic uploads of proprietary formats using scripts. Raw data from the 3T Skyra scanner is also sent to a server and then archived to LaRDS on request from projects. This can then be reconstructed and post-processed with different algorithms to those available on the scanner.\n<\/p><p>For large datasets that are required to be accessed often, digital object identifiers (DOIs) and digital handles are being implemented in DaRIS as long-lived references to the datasets. \n<\/p>\n<h3><span class=\"mw-headline\" id=\"User_interaction\">User interaction<\/span><\/h3>\n<p>Researchers access data stored in DaRIS and XNAT using a web portal, client programs and scripts (Figure 3). Both DaRIS and XNAT implement strong security protocols with role based authenticated access to restrict unintended access. Layered on the permission model of Mediaflux, DaRIS provides four layers of role-based authorisation to protect data objects and services. Each project in DaRIS belongs to users with role-based access that determines their access to assets and services: (i) the nominated project administrator(s) can control access to the project and modify project team\/roles, (ii) subject administrator(s) can create and administer subjects, (iii) user(s) can access all research data but not subject identity (where that information has optionally been directly entered by the project or subject administrator - by default subject identity is not stored in DaRIS), and (iv) guest(s) can access meta-data only. \n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"fe2275fc86c6a88676ed0eedff42da16\"><img alt=\"Fig3 Nguyen HealthInfoSciSys2015 3-Suppl1.jpg\" src=\"https:\/\/www.limswiki.org\/images\/f\/f8\/Fig3_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 3. User interaction.<\/b> Illustration of the different ways the user can interact with the informatics system.<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>DaRIS can operate in a distributed environment and projects can be stored and federated over multiple servers. Since the location of assets associated with data and meta-data is largely transparent to the users and accessible from anywhere through mechanisms including distributed queries, remote access and replication, imaging data stored on DaRIS can be accessed from researchers at different institutions using client programs, command line tools and web portals. As a result, DaRIS provides an efficient way to access data across and within large collaborations. Authenticated users can download data easily using the DaRIS web portal as shown in Figure 4. They can download imaging data of studies, subjects or even an entire project using \"shopping carts\", and transcoding to popular medical image formats can be applied prior to download. Users can also find and download their data with client scripts which provide a convenient way to process imaging data inside batch scripts or programs developed in their preferred programming languages. For example, users of the Multi-modal Australian ScienceS Imaging and Visualisation Environment (MASSIVE) (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.massive.org.au\" target=\"_blank\">http:\/\/www.massive.org.au<\/a>) high performance computing facility can access and process imaging data that is downloaded from DaRIS. \n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg\" class=\"image wiki-link\" target=\"_blank\" data-key=\"f6b21e7cb23f7196177a6427fbd69032\"><img alt=\"Fig4 Nguyen HealthInfoSciSys2015 3-Suppl1.jpg\" src=\"https:\/\/www.limswiki.org\/images\/f\/fd\/Fig4_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"> <blockquote><b>Figure 4. User interface for DaRIS.<\/b> The web based user interface of DaRIS showing the main interface panel in (a) and the \"cart\" functionality in (b).<\/blockquote>\n<\/td><\/tr>\n<\/table>\n<\/td><\/tr><\/table>\n<p>XNAT can control the access of an individual user down to the single record level by using a hybrid XML relational database structure. When a user retrieves data that are stored in the relational database, XNAT checks whether or not the user is permitted access to the data by using the security protocols defined in XML data model. The XML security protocol is defined by selecting one or more security fields that are assigned one or more allowed values in each user's account. XNAT project administrators can assign access rules for users of the project using administrative tools included in the XNAT web application. XNAT also provides a very flexible HTTP\/REST based API for access, control and upload of data. Due to the flexibility of this API and the ability to program XNAT in a language-independent manner, XNAT is a preferred platform for projects that perform significant sequences of automated steps in data management (including on ingest).\n<\/p><p>Non-DICOM and processed data can be uploaded via the DaRIS and XNAT portals, and using scripts. For DaRIS, post-processed data is added at the same level in the hierarchy as the originating data, but is tagged as being post-processed and referenced to the original dataset. Processed data can originate from more than one data set, as would be the case for a cohort based atlas image in a multi-subject study. In XNAT, post-processed data are tagged as reconstructions or image assessments (subclass of scans). Reconstructions are post-processed raw data or image data that are not derivatives. Image assessments are derivative images or statistics. \n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h2>\n<p>Our system, implemented over the period October 2011 to July 2012 and refined in the intervening time, successfully realises the core capability requirements outlined above. All human imaging projects presently being undertaken at MBI on the Skyra 3T scanner are using the MBI imaging informatics system - and specifically the DaRIS backend - for the management, archive and retrieval of MR images. Many non-human imaging projects, using e.g. the small-bore high-field MR scanner or the small-bore microCT\/PET instrument, are also using the system as it provides a simple and reliable image management platform. Additionally, several large projects are being carried out at Monash University using data acquired elsewhere but federated into the Monash University DaRIS system. Large cohort longitudinal studies commenced at MBI will use the imaging informatics system from the outset. Presently (June 2014) there are nearly 100 distinct research projects registered in the system, and 110 users. The total compressed size of ingested data exceeds 1 TB. While this may be considered a relatively small volume, the uncompressed data size is 3-5 times this number. We expect significant growth as large imaging studies get underway and processed data and provenace information are archived together with the raw acquired datasets.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h2>\n<p>Biomedical imaging studies, especially multi-modal, longitudinal studies of large subject cohorts, generate large collections of data that need to be stored, archived and accessed. Contemporary mid-range MRI based studies can easily accumulate terabytes of data annually. The appropriate use of meta-data, and the recording of provenance for processed data collections, is critical in enabling integrative science, as well as establishing the long term quality and value of the data. The integration of image informatics platforms with the scientific instrumentation, with research quality archival data stores, and with performant processing systems (e.g. compute clusters) is critical in meeting the challenge of extracting new knowledge from biomedical imaging research data.\n<\/p><p>The system implemented at MBI and described in this article, caters for the needs of a large research imaging centre that generates data from human and non-human imaging experiments. The data is made available to researchers using two informatics platforms, namely DaRIS and XNAT. DaRIS is a project that, while ready for use, is undergoing active development and addition of features. Our close relationship with the DaRIS developers allows us to explore and modify the behaviour of the system to suit, and to provide input on future development directions. Our choice to support XNAT as well is driven by user demand, but effectively positions us to undertake a direct evaluation of the relative strengths, weaknesses, and future opportunities for both systems. In particular, we are very interested in developing interoperability between DaRIS and XNAT to allow flexibility in choice of tool for accessing and manipulating archival image and meta-data. We are also developing a file system based informatics platform based on the python classes. This will give users the ability to either cache their data or to use the python tools and workflows using data from a local filesystem. \n<\/p><p>Currently, the DaRIS platform is being developed to natively support additional data formats, both standardised and vendor specific formats. This work will enable the automated extraction of relevant meta-data from the supported formats, and the display of image \"thumbnails\" in the web interface. Another avenue of development is focused on workflows for processing data. Workflows can be programmed in XNAT already but are restricted to run on the XNAT host. Moreover, the pipeline descriptions are programmed using an XML type language specific to XNAT. To alleviate these issues, workflows in DaRIS are currently being developed using the established and well known workflow engines NIMROD<sup id=\"rdp-ebb-cite_ref-AbramsonParam11_21-0\" class=\"reference\"><a href=\"#cite_note-AbramsonParam11-21\" rel=\"external_link\">[21]<\/a><\/sup> and KEPLER<sup id=\"rdp-ebb-cite_ref-LudascherSci06_22-0\" class=\"reference\"><a href=\"#cite_note-LudascherSci06-22\" rel=\"external_link\">[22]<\/a><\/sup> and will be designed to distribute computational workload across HPC systems such as MASSIVE and the NeCTAR (<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nectar.org.au\" target=\"_blank\">http:\/\/www.nectar.org.au<\/a>) Research Cloud. The automatic provenance tracking already available in Kepler brings a significant advantage presently lacking in XNAT workflows. \n<\/p><p>Within the context of workflows, we are exploring the choice of \"push\" versus \"pull\" processing. The work described above is focussed on push workflows, where (usually implicit) actions within the informatics system initiate processing of data: the data is pushed out to a processing system, the data are processed, and the results ingested. This is appropriate for wholly automated processing of large, rigidly self consistent data sets (i.e. many images that are acquired identically and need to be processed identically), with high throughput. However, for smaller bespoke projects, the pull style of workflow may be more suitable, and in particular enables mostly automated workflows but with manual intervention and inspection. To many users the pull workflow is more natural and controllable. The python tools that have been developed are utilised to develop \"pull\" type workflows that can be run independently of the informatics system and not tied to any computation platform. For example we have started providing nipype workflows tailored for acquisitions on our scanner for typical neuroimaging tasks. Nipype is workflow\/pipeline engine written in python specifically for the medical imaging\/neuroimaging community.<sup id=\"rdp-ebb-cite_ref-GorgolewskiNip11_23-0\" class=\"reference\"><a href=\"#cite_note-GorgolewskiNip11-23\" rel=\"external_link\">[23]<\/a><\/sup> These workflows are paired with the python tools to download appropriate datasets from projects, perform the task and uploaded processed data back onto the informatics system. An example of this is the Freesurfer recon_all workflow<sup id=\"rdp-ebb-cite_ref-HarvardFreeSurfer_14-2\" class=\"reference\"><a href=\"#cite_note-HarvardFreeSurfer-14\" rel=\"external_link\">[14]<\/a><\/sup> that segments brain MRI images. Another example is the preprocessing of functional MRI data to correct for head-motion and distortion. The advantage of the pull type of workflows is that they are distributed and not confined to the hardware of the informatics system. These allow them to be run from any computer supporting the tools used in the workflow with a cost of data transfer to and from the informatics system. \n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>A research imaging data management system based on DaRIS and XNAT has been designed and implemented to enable researchers to acquire, manage and analyse large, longitudinal biomedical imaging datasets. The system provides stable long-term storage data and sophisticated support tools for multi-modality biomedical imaging research. Current developments of DaRIS include enhancements to integrate scientific and computational push and pull workflows with the managed data repository. In future work, imaging data will be integrated with the Australian National Data Service (ANDS) registry to make better use of data outputs, and biomedical atlases to provide more quantitative information.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Abbreviations\">Abbreviations<\/span><\/h2>\n<p>API: application programming interface \n<\/p><p>CT: computer tomography\n<\/p><p>DaRIS: distributed and reflective informatics system\n<\/p><p>DICOM: digital imaging and communications in medicine\n<\/p><p>DOI: digital object identifier\n<\/p><p>EEG: Electroencephalography\n<\/p><p>GB: gigabyte\n<\/p><p>HTTP: hypertext transfer protocol\n<\/p><p>HPC: high performance computing\n<\/p><p>LaRDS: large research data storage\n<\/p><p>MB: megabyte\n<\/p><p>MBI: Monash Biomedical Imaging\n<\/p><p>MRI: magnetic resonance imaging\n<\/p><p>NiFTI: neuroimaging informatics technology initiative\n<\/p><p>PACS: picture archiving and communication system\n<\/p><p>PSSD: project-subject-study-data\n<\/p><p>RAID: redundant array of independent disks\n<\/p><p>TB: terabyte\n<\/p><p>TCL: tool command language\n<\/p><p>VeRSI: Victorian e-research strategic initiative\n<\/p><p>XML: extensible markup language\n<\/p><p>XNAT: extensible neuroimaging archive toolkit\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Competing_interests\">Competing interests<\/span><\/h2>\n<p>The authors declare that they have no competing interests.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Declarations\">Declarations<\/span><\/h2>\n<p>The authors would like to thank the Monash Biomedical Imaging, Monash University, Melbourne, Australia for financial support.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Authors.27_contributions\">Authors' contributions<\/span><\/h2>\n<p>GFE, DGB and PR developed the background, designed the method and analysed the results. TDN, PR and DGB implemented the methods and provided figures and data. GFE was the leader of this work. All authors read and approved the final manuscript.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>We thank N. Killeen and W. Liu (University of Melbourne) and J. Lohrey (Arcitecta) for developing and supporting the DaRIS code and web portal. We thank N. McPhee and S. Dart (Monash University) for local support of DaRIS and the Monash LaRDS infrastructure and we thank R. Keil and C. Chow for early designs of the MBI data flow. The DaRIS Method Builder was developed by A. Glenn, S. Izzo, R. Rothwell and S. Bennett (VeRSI). We thank W. Goscinski and P. McIntosh (Monash University) and C. West (VPAC) for supporting interoperation of DaRIS with the MASSIVE facility. T. D. Nguyen acknowledges support from the National Imaging Facility. The VLSCI's Life Sciences Computation Centre is a collaboration between Melbourne, Monash and La Trobe Universities and an initiative of the Victorian Government, Australia. The authors would like to thank the Monash Biomedical Imaging, Monash University, Melbourne, Australia for financial support.\n<\/p><p>This article has been published as part of Health Information Science and Systems Volume 3 Supplement 1, 2015: Proceedings of the Health Informatics Society of Australia Big Data Conference (HISA 2013). 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(2009). \"The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease\". <i>International Psychogeriatrics<\/i> <b>21<\/b> (4): 672-87. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1017%2FS1041610209009405\" target=\"_blank\">10.1017\/S1041610209009405<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19470201\" target=\"_blank\">19470201<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Australian+Imaging%2C+Biomarkers+and+Lifestyle+%28AIBL%29+study+of+aging%3A+methodology+and+baseline+characteristics+of+1112+individuals+recruited+for+a+longitudinal+study+of+Alzheimer%27s+disease&rft.jtitle=International+Psychogeriatrics&rft.aulast=Ellis%2C+K.A.%3B+Bush%2C+A.I.%3B+Darby%2C+D.+et+al.&rft.au=Ellis%2C+K.A.%3B+Bush%2C+A.I.%3B+Darby%2C+D.+et+al.&rft.date=2009&rft.volume=21&rft.issue=4&rft.pages=672-87&rft_id=info:doi\/10.1017%2FS1041610209009405&rft_id=info:pmid\/19470201&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-MuellerWays05-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-MuellerWays05_8-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mueller, S.G.; Weiner, M.W.; Thal, L.J. et al. (2005). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1864941\" target=\"_blank\">\"Ways toward an early diagnosis in Alzheimer's disease: the Alzheimer's Disease Neuroimaging Initiative (ADNI)\"<\/a>. <i>Alzheimer's & Dementia<\/i> <b>1<\/b> (1): 55\u201366. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jalz.2005.06.003\" target=\"_blank\">10.1016\/j.jalz.2005.06.003<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1864941\/\" target=\"_blank\">PMC1864941<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17476317\" target=\"_blank\">17476317<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1864941\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC1864941<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Ways+toward+an+early+diagnosis+in+Alzheimer%27s+disease%3A+the+Alzheimer%27s+Disease+Neuroimaging+Initiative+%28ADNI%29&rft.jtitle=Alzheimer%27s+%26+Dementia&rft.aulast=Mueller%2C+S.G.%3B+Weiner%2C+M.W.%3B+Thal%2C+L.J.+et+al.&rft.au=Mueller%2C+S.G.%3B+Weiner%2C+M.W.%3B+Thal%2C+L.J.+et+al.&rft.date=2005&rft.volume=1&rft.issue=1&rft.pages=55%E2%80%9366&rft_id=info:doi\/10.1016%2Fj.jalz.2005.06.003&rft_id=info:pmc\/PMC1864941&rft_id=info:pmid\/17476317&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC1864941&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-HofmanTheRott09-9\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-HofmanTheRott09_9-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hofman, A.; Breteler, M.M.B.; van Duijn, C.M. et al. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2744826\" target=\"_blank\">\"The Rotterdam Study: 2010 objectives and design update\"<\/a>. <i>European Journal of Epidemiology<\/i> <b>24<\/b> (9): 553-72. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs10654-009-9386-z\" target=\"_blank\">10.1007\/s10654-009-9386-z<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2744826\/\" target=\"_blank\">PMC2744826<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19728115\" target=\"_blank\">19728115<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2744826\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2744826<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Rotterdam+Study%3A+2010+objectives+and+design+update&rft.jtitle=European+Journal+of+Epidemiology&rft.aulast=Hofman%2C+A.%3B+Breteler%2C+M.M.B.%3B+van+Duijn%2C+C.M.+et+al.&rft.au=Hofman%2C+A.%3B+Breteler%2C+M.M.B.%3B+van+Duijn%2C+C.M.+et+al.&rft.date=2009&rft.volume=24&rft.issue=9&rft.pages=553-72&rft_id=info:doi\/10.1007%2Fs10654-009-9386-z&rft_id=info:pmc\/PMC2744826&rft_id=info:pmid\/19728115&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2744826&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LinkertMeta10-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-LinkertMeta10_10-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Linkert, M.; Rueden, C.T.; Allan, C. et al. (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2878938\" target=\"_blank\">\"Metadata matters: access to image data in the real world\"<\/a>. <i>Journal of Cell Biology<\/i> <b>189<\/b> (5): 777-82. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1083%2Fjcb.201004104\" target=\"_blank\">10.1083\/jcb.201004104<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2878938\/\" target=\"_blank\">PMC2878938<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20513764\" target=\"_blank\">20513764<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2878938\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2878938<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Metadata+matters%3A+access+to+image+data+in+the+real+world&rft.jtitle=Journal+of+Cell+Biology&rft.aulast=Linkert%2C+M.%3B+Rueden%2C+C.T.%3B+Allan%2C+C.+et+al.&rft.au=Linkert%2C+M.%3B+Rueden%2C+C.T.%3B+Allan%2C+C.+et+al.&rft.date=2010&rft.volume=189&rft.issue=5&rft.pages=777-82&rft_id=info:doi\/10.1083%2Fjcb.201004104&rft_id=info:pmc\/PMC2878938&rft_id=info:pmid\/20513764&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2878938&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-BryanTheBen99-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-BryanTheBen99_11-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bryan, S.; Weatherburn, G.C.; Watkins, J.R.; Buxton, M.J. et al. 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Retrieved 17 June 2014<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=FreeSurfer&rft.atitle=&rft.pub=Harvard+University&rft_id=http%3A%2F%2Fsurfer.nmr.mgh.harvard.edu%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-DFWG_NIfTI-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-DFWG_NIfTI_15-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/nifti.nimh.nih.gov\/\" target=\"_blank\">\"NIfTI: Neuroimaging Informatics Technology Initiative\"<\/a>. 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Retrieved 17 June 2014<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=NIfTI%3A+Neuroimaging+Informatics+Technology+Initiative&rft.atitle=&rft.pub=Data+Format+Working+Group&rft_id=http%3A%2F%2Fnifti.nimh.nih.gov%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-MarcusTheExt07-16\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-MarcusTheExt07_16-0\" rel=\"external_link\">16.0<\/a><\/sup> <sup><a href=\"#cite_ref-MarcusTheExt07_16-1\" rel=\"external_link\">16.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Marcus, D.S.; Olsen, T.R.; Ramaratnam, M.; Buckner, R.L. et al. (2007). \"The Extensible Neuroimaging Archive Toolkit: an informatics platform for managing, exploring, and sharing neuroimaging data\". <i>Neuroinformatics<\/i> <b>5<\/b> (1): 11-34. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1385%2FNI%3A5%3A1%3A11\" target=\"_blank\">10.1385\/NI:5:1:11<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17426351\" target=\"_blank\">17426351<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Extensible+Neuroimaging+Archive+Toolkit%3A+an+informatics+platform+for+managing%2C+exploring%2C+and+sharing+neuroimaging+data&rft.jtitle=Neuroinformatics&rft.aulast=Marcus%2C+D.S.%3B+Olsen%2C+T.R.%3B+Ramaratnam%2C+M.%3B+Buckner%2C+R.L.+et+al.&rft.au=Marcus%2C+D.S.%3B+Olsen%2C+T.R.%3B+Ramaratnam%2C+M.%3B+Buckner%2C+R.L.+et+al.&rft.date=2007&rft.volume=5&rft.issue=1&rft.pages=11-34&rft_id=info:doi\/10.1385%2FNI%3A5%3A1%3A11&rft_id=info:pmid\/17426351&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LohreyAnInt09-17\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-LohreyAnInt09_17-0\" rel=\"external_link\">17.0<\/a><\/sup> <sup><a href=\"#cite_ref-LohreyAnInt09_17-1\" rel=\"external_link\">17.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Lohrey, J.M.; Killeen, N.E.B.; Egan, G.F. et al. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2715266\" target=\"_blank\">\"An integrated object model and method framework for subject-centric e-Research applications\"<\/a>. <i>Frontiers in Neuroinformatics<\/i> <b>3<\/b>: 19. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Fneuro.11.019.2009\" target=\"_blank\">10.3389\/neuro.11.019.2009<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2715266\/\" target=\"_blank\">PMC2715266<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19636389\" target=\"_blank\">19636389<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2715266\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2715266<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=An+integrated+object+model+and+method+framework+for+subject-centric+e-Research+applications&rft.jtitle=Frontiers+in+Neuroinformatics&rft.aulast=Lohrey%2C+J.M.%3B+Killeen%2C+N.E.B.%3B+Egan%2C+G.F.+et+al.&rft.au=Lohrey%2C+J.M.%3B+Killeen%2C+N.E.B.%3B+Egan%2C+G.F.+et+al.&rft.date=2009&rft.volume=3&rft.pages=19&rft_id=info:doi\/10.3389%2Fneuro.11.019.2009&rft_id=info:pmc\/PMC2715266&rft_id=info:pmid\/19636389&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2715266&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-BookNeuro13-18\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-BookNeuro13_18-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Book, G.A.; Anderson, B.M.; Stevens, M.C.; Glahn, D.C.; Assaf, M.; Pearlson, G.D. (2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3864015\" target=\"_blank\">\"Neuroinformatics Database (NiDB)--a modular, portable database for the storage, analysis, and sharing of neuroimaging data\"<\/a>. <i>Neuroinformatics<\/i> <b>11<\/b> (4): 495-505. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs12021-013-9194-1\" target=\"_blank\">10.1007\/s12021-013-9194-1<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3864015\/\" target=\"_blank\">PMC3864015<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23912507\" target=\"_blank\">23912507<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3864015\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3864015<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Neuroinformatics+Database+%28NiDB%29--a+modular%2C+portable+database+for+the+storage%2C+analysis%2C+and+sharing+of+neuroimaging+data&rft.jtitle=Neuroinformatics&rft.aulast=Book%2C+G.A.%3B+Anderson%2C+B.M.%3B+Stevens%2C+M.C.%3B+Glahn%2C+D.C.%3B+Assaf%2C+M.%3B+Pearlson%2C+G.D.&rft.au=Book%2C+G.A.%3B+Anderson%2C+B.M.%3B+Stevens%2C+M.C.%3B+Glahn%2C+D.C.%3B+Assaf%2C+M.%3B+Pearlson%2C+G.D.&rft.date=2013&rft.volume=11&rft.issue=4&rft.pages=495-505&rft_id=info:doi\/10.1007%2Fs12021-013-9194-1&rft_id=info:pmc\/PMC3864015&rft_id=info:pmid\/23912507&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC3864015&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-VanHornIsIt09-19\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-VanHornIsIt09_19-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Van Horn, J.D.; Toga, A.W. (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2754579\" target=\"_blank\">\"Is it Time to Re-Prioritize Neuroimaging Databases and Digital Repositories?\"<\/a>. <i>NeuroImage<\/i> <b>47<\/b> (4): 1720-34. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.neuroimage.2009.03.086\" target=\"_blank\">10.1016\/j.neuroimage.2009.03.086<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2754579\/\" target=\"_blank\">PMC2754579<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19371790\" target=\"_blank\">19371790<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2754579\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2754579<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Is+it+Time+to+Re-Prioritize+Neuroimaging+Databases+and+Digital+Repositories%3F&rft.jtitle=NeuroImage&rft.aulast=Van+Horn%2C+J.D.%3B+Toga%2C+A.W.&rft.au=Van+Horn%2C+J.D.%3B+Toga%2C+A.W.&rft.date=2009&rft.volume=47&rft.issue=4&rft.pages=1720-34&rft_id=info:doi\/10.1016%2Fj.neuroimage.2009.03.086&rft_id=info:pmc\/PMC2754579&rft_id=info:pmid\/19371790&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2754579&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-MacKenzieProv08-20\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-MacKenzieProv08_20-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">MacKenzie-Graham, A.J.; Van Horn, J.D.; Woods, R.P.; Crawford, K.L.; Toga, A.W. (2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2664747\" target=\"_blank\">\"Provenance in neuroimaging\"<\/a>. <i>NeuroImage<\/i> <b>42<\/b> (1): 178-95. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.neuroimage.2008.04.186\" target=\"_blank\">10.1016\/j.neuroimage.2008.04.186<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2664747\/\" target=\"_blank\">PMC2664747<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18519166\" target=\"_blank\">18519166<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2664747\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2664747<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Provenance+in+neuroimaging&rft.jtitle=NeuroImage&rft.aulast=MacKenzie-Graham%2C+A.J.%3B+Van+Horn%2C+J.D.%3B+Woods%2C+R.P.%3B+Crawford%2C+K.L.%3B+Toga%2C+A.W.&rft.au=MacKenzie-Graham%2C+A.J.%3B+Van+Horn%2C+J.D.%3B+Woods%2C+R.P.%3B+Crawford%2C+K.L.%3B+Toga%2C+A.W.&rft.date=2008&rft.volume=42&rft.issue=1&rft.pages=178-95&rft_id=info:doi\/10.1016%2Fj.neuroimage.2008.04.186&rft_id=info:pmc\/PMC2664747&rft_id=info:pmid\/18519166&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC2664747&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-AbramsonParam11-21\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-AbramsonParam11_21-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Abramson, D.; Bethwaite, B.; Enticott, C.; Garic, S.; Peachey, T. (2011). \"Parameter Exploration in Science and Engineering Using Many-Task Computing\". <i>IEEE Transactions on Parallel and Distributed Systems<\/i> <b>22<\/b> (6): 960-973. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FTPDS.2010.177\" target=\"_blank\">10.1109\/TPDS.2010.177<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Parameter+Exploration+in+Science+and+Engineering+Using+Many-Task+Computing&rft.jtitle=IEEE+Transactions+on+Parallel+and+Distributed+Systems&rft.aulast=Abramson%2C+D.%3B+Bethwaite%2C+B.%3B+Enticott%2C+C.%3B+Garic%2C+S.%3B+Peachey%2C+T.&rft.au=Abramson%2C+D.%3B+Bethwaite%2C+B.%3B+Enticott%2C+C.%3B+Garic%2C+S.%3B+Peachey%2C+T.&rft.date=2011&rft.volume=22&rft.issue=6&rft.pages=960-973&rft_id=info:doi\/10.1109%2FTPDS.2010.177&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-LudascherSci06-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-LudascherSci06_22-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Lud\u00e4scher, B.; Altintas, I.; Berkley, C. et al. 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Special issue: workflow in grid systems\". <i>Concurrency and Computation: Practice & Experience<\/i> <b>18<\/b> (10): 1039-1065. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fcpe.v18%3A10\" target=\"_blank\">10.1002\/cpe.v18:10<\/a>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Scientific+workflow+management+and+the+Kepler+system.+Special+issue%3A+workflow+in+grid+systems&rft.jtitle=Concurrency+and+Computation%3A+Practice+%26+Experience&rft.aulast=Lud%C3%A4scher%2C+B.%3B+Altintas%2C+I.%3B+Berkley%2C+C.+et+al.&rft.au=Lud%C3%A4scher%2C+B.%3B+Altintas%2C+I.%3B+Berkley%2C+C.+et+al.&rft.date=2006&rft.volume=18&rft.issue=10&rft.pages=1039-1065&rft_id=info:doi\/10.1002%2Fcpe.v18%3A10&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<li id=\"cite_note-GorgolewskiNip11-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-GorgolewskiNip11_23-0\" rel=\"external_link\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gorgolewski, K.; Burns, C.D.; Madison, C. et al. (2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3159964\" target=\"_blank\">\"Nipype: a flexible, lightweight and extensible neuroimaging data processing framework in python\"<\/a>. <i>Frontiers in Neuroinformatics<\/i> <b>5<\/b>: 13. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" target=\"_blank\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffninf.2011.00013\" target=\"_blank\">10.3389\/fninf.2011.00013<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" target=\"_blank\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3159964\/\" target=\"_blank\">PMC3159964<\/a>. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" target=\"_blank\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21897815\" target=\"_blank\">21897815<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3159964\" target=\"_blank\">http:\/\/www.pubmedcentral.nih.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3159964<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Nipype%3A+a+flexible%2C+lightweight+and+extensible+neuroimaging+data+processing+framework+in+python&rft.jtitle=Frontiers+in+Neuroinformatics&rft.aulast=Gorgolewski%2C+K.%3B+Burns%2C+C.D.%3B+Madison%2C+C.+et+al.&rft.au=Gorgolewski%2C+K.%3B+Burns%2C+C.D.%3B+Madison%2C+C.+et+al.&rft.date=2011&rft.volume=5&rft.pages=13&rft_id=info:doi\/10.3389%2Ffninf.2011.00013&rft_id=info:pmc\/PMC3159964&rft_id=info:pmid\/21897815&rft_id=http%3A%2F%2Fwww.pubmedcentral.nih.gov%2Farticlerender.fcgi%3Ftool%3Dpmcentrez%26artid%3DPMC3159964&rfr_id=info:sid\/en.wikipedia.org:Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\"><span style=\"display: none;\"> <\/span><\/span><\/span>\n<\/li>\n<\/ol><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20181214192201\nCache expiry: 86400\nDynamic content: false\nCPU time usage: 0.610 seconds\nReal time usage: 0.646 seconds\nPreprocessor visited node count: 19302\/1000000\nPreprocessor generated node count: 32869\/1000000\nPost\u2010expand include size: 163134\/2097152 bytes\nTemplate argument size: 51416\/2097152 bytes\nHighest expansion depth: 18\/40\nExpensive parser function count: 0\/100\n-->\n\n<!-- \nTransclusion expansion time report (%,ms,calls,template)\n100.00% 606.366 1 - -total\n 84.50% 512.370 1 - Template:Reflist\n 74.14% 449.542 23 - Template:Citation\/core\n 70.94% 430.177 20 - Template:Cite_journal\n 10.72% 65.028 45 - Template:Citation\/identifier\n 10.68% 64.735 1 - Template:Infobox_journal_article\n 10.25% 62.149 1 - Template:Infobox\n 7.35% 44.580 3 - Template:Cite_web\n 6.14% 37.207 80 - Template:Infobox\/row\n 4.00% 24.260 23 - Template:Citation\/make_link\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:7926-0!*!0!!en!5!* and timestamp 20181214192200 and revision id 23640\n -->\n<\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository\">https:\/\/www.limswiki.org\/index.php\/Journal:Design,_implementation_and_operation_of_a_multimodality_research_imaging_informatics_repository<\/a><\/div>\n\t\t\t\t\t\t\t\t\t\t<!-- end content -->\n\t\t\t\t\t\t\t\t\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t\t<!-- end of the left (by default at least) column -->\n\t\t<div class=\"visualClear\"><\/div>\n\t\t\t\t\t\n\t\t<\/div>\n\t\t\n\n<\/body>","de90eb3652231af7bd081d7eedc00c72_images":["https:\/\/www.limswiki.org\/images\/6\/64\/Fig1_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg","https:\/\/www.limswiki.org\/images\/5\/5e\/Fig2_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg","https:\/\/www.limswiki.org\/images\/f\/f8\/Fig3_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg","https:\/\/www.limswiki.org\/images\/f\/fd\/Fig4_Nguyen_HealthInfoSciSys2015_3-Suppl1.jpg"],"de90eb3652231af7bd081d7eedc00c72_timestamp":1544815320,"81279589d61b779aba171baca35b1086":{"type":"chapter","title":"1. Laboratory and bioinformatics","key":"81279589d61b779aba171baca35b1086"}},"link":"https:\/\/www.limswiki.org\/index.php\/Book:LIMSjournal_-_Spring_2016","price_currency":"","price_amount":"","book_size":"","download_url":"https:\/\/www.limsforum.com?ebb_action=book_download&book_id=78060","language":"","cta_button_content":"","toc":[{"type":"chapter","name":"1. 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LIMSjournal - Spring 2016
Volume 2, Issue 1
Editor: Shawn Douglas
Publisher: LabLynx Press
Copyright LabLynx Inc. All rights reserved.